Filamentary devices for treatment of vascular defects

ABSTRACT

Methods for treatment of a cerebral aneurysm within a cerebral vasculature of a patient are described. A microcatheter and a device for treatment of the aneurysm are provided. The device is a self-expanding resilient permeable shell having a plurality of elongate resilient filaments with a woven structure. The plurality of filaments includes small and large filaments. The filaments are bundled and secured to each other at a proximal end. A ratio of the total cross-sectional area of small filaments to the total cross-sectional area of large filaments may be between 0.56 and 1.89. The distal end of the microcatheter is advanced to a region of interest within a cerebral artery. The device is advanced through the lumen and out of the distal end of the microcatheter such that the permeable shell deploys and expands within the cerebral aneurysm. The microcatheter is then withdrawn from the cerebral artery.

RELATED APPLICATIONS

This application is a continuation of and claims priority from U.S.patent application Ser. No. 13/771,632, filed Feb. 20, 2013, which is acontinuation of and claims priority from U.S. patent application Ser.No. 12/434,465, filed May 1, 2009, by Cox et al., titled “FilamentaryDevices for Treatment of Vascular Defects”, now issued as U.S. Pat. No.9,597,087, which claims the benefit of priority under 35 U.S.C. section119(e) from U.S. Provisional Patent Application No. 61/050,124 filed May2, 2008, by Cox et al. titled “Filamentary Devices for Treatment ofVascular Defects”, all of which are incorporated by reference herein intheir entirety.

This application is related to Provisional Patent Application Ser. No.61/044,822, filed Apr. 14, 2008, entitled “Methods and Devices forTreatment of Vascular Defects”, naming Brian J. Cox et al. as inventors,Provisional Patent Application Ser. No. 60/941,928, filed on Jun. 4,2007, entitled “Method and Apparatus for Treatment of a VascularDefect,” naming Brian J. Cox et al. as inventors, U.S. ProvisionalPatent Application Ser. No. 60/094,683, filed on Jul. 9, 2007, entitled“Vascular Occlusion Devices,” naming Brian J. Cox et al. as inventors,and U.S. Provisional Patent Application Ser. No. 60/097,366, filed onSep. 11, 2007, entitled “Method and Apparatus for Treatment of aVascular Defect,” naming Dean Schaefer et al. as inventors,International PCT Patent Application No. PCT/US2008/065694, publishedDec. 11, 2008, number WO 2008/151204, filed Jun. 3, 2008, entitled“Methods and Devices for Treatment of Vascular Defects”, naming Brian J.Cox et al. as inventors, which are all incorporated by reference hereinin their entirety.

FIELD OF THE INVENTION

Embodiments of devices and methods herein are directed to blocking aflow of fluid through a tubular vessel or into a small interior chamberof a saccular cavity or vascular defect within a mammalian body. Morespecifically, embodiments herein are directed to devices and methods fortreatment of a vascular defect of a patient including some embodimentsdirected specifically to the treatment of cerebral aneurysms ofpatients.

BACKGROUND

The mammalian circulatory system is comprised of a heart, which acts asa pump, and a system of blood vessels which transport the blood tovarious points in the body. Due to the force exerted by the flowingblood on the blood vessel the blood vessels may develop a variety ofvascular defects. One common vascular defect known as an aneurysmresults from the abnormal widening of the blood vessel. Typically,vascular aneurysms are formed as a result of the weakening of the wallof a blood vessel and subsequent ballooning and expansion of the vesselwall. If, for example, an aneurysm is present within an artery of thebrain, and the aneurysm should burst with resulting cranialhemorrhaging, death could occur.

Surgical techniques for the treatment of cerebral aneurysms typicallyinvolve a craniotomy requiring creation of an opening in the skull ofthe patient through which the surgeon can insert instruments to operatedirectly on the patient's brain. For some surgical approaches, the brainmust be retracted to expose the parent blood vessel from which theaneurysm arises. Once access to the aneurysm is gained, the surgeonplaces a clip across the neck of the aneurysm thereby preventingarterial blood from entering the aneurysm. Upon correct placement of theclip the aneurysm will be obliterated in a matter of minutes. Surgicaltechniques may be effective treatment for many aneurysms. Unfortunately,surgical techniques for treating these types of conditions include majorinvasive surgical procedures which often require extended periods oftime under anesthesia involving high risk to the patient. Suchprocedures thus require that the patient be in generally good physicalcondition in order to be a candidate for such procedures.

Various alternative and less invasive procedures have been used to treatcerebral aneurysms without resorting to major surgery. Some suchprocedures involve the delivery of embolic or filling materials into ananeurysm. The delivery of such vaso-occlusion devices or materials maybe used to promote hemostasis or fill an aneurysm cavity entirely.Vaso-occlusion devices may be placed within the vasculature of the humanbody, typically via a catheter, either to block the flow of bloodthrough a vessel with an aneurysm through the formation of an embolus orto form such an embolus within an aneurysm stemming from the vessel. Avariety of implantable, coil-type vaso-occlusion devices are known. Thecoils of such devices may themselves be formed into a secondary coilshape, or any of a variety of more complex secondary shapes.Vaso-occlusive coils are commonly used to treat cerebral aneurysms butsuffer from several limitations including poor packing density,compaction due to hydrodynamic pressure from blood flow, poor stabilityin wide-necked aneurysms and complexity and difficulty in the deploymentthereof as most aneurysm treatments with this approach require thedeployment of multiple coils.

Another approach to treating aneurysms without the need for invasivesurgery involves the placement of sleeves or stents into the vessel andacross the region where the aneurysm occurs. Such devices maintain bloodflow through the vessel while reducing blood pressure applied to theinterior of the aneurysm. Certain types of stents are expanded to theproper size by inflating a balloon catheter, referred to as balloonexpandable stents, while other stents are designed to elastically expandin a self-expanding manner. Some stents are covered typically with asleeve of polymeric material called a graft to form a stent-graft.Stents and stent-grafts are generally delivered to a preselectedposition adjacent a vascular defect through a delivery catheter. In thetreatment of cerebral aneurysms, covered stents or stent-grafts haveseen very limited use due to the likelihood of inadvertent occlusion ofsmall perforator vessels that may be near the vascular defect beingtreated.

In addition, current uncovered stents are generally not sufficient as astand-alone treatment. In order for stents to fit through themicrocatheters used in small cerebral blood vessels, their density isusually reduced such that when expanded there is only a small amount ofstent structure bridging the aneurysm neck. Thus, they do not blockenough flow to cause clotting of the blood in the aneurysm and are thusgenerally used in combination with vaso-occlusive devices, such as thecoils discussed above, to achieve aneurysm occlusion.

A number of aneurysm neck bridging devices with defect spanning portionsor regions have been attempted; however, none of these devices have hada significant measure of clinical success or usage. A major limitationin their adoption and clinical usefulness is the inability to positionthe defect spanning portion to assure coverage of the neck. Existingstent delivery systems that are neurovascular compatible (i.e.deliverable through a microcatheter and highly flexible) do not have thenecessary rotational positioning capability. Another limitation of manyaneurysm bridging devices described in the prior art is the poorflexibility. Cerebral blood vessels are tortuous and a high degree offlexibility is required for effective delivery to most aneurysmlocations in the brain.

What has been needed are devices and methods for delivery and use insmall and tortuous blood vessels that can substantially block the flowof blood into an aneurysm, such as a cerebral aneurysm, with a decreasedrisk of inadvertent aneurysm rupture or blood vessel wall damage. Inaddition, what has been needed are methods and devices suitable forblocking blood flow in cerebral aneurysms over an extended period oftime without a significant risk of deformation, compaction ordislocation.

SUMMARY

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell having a proximalend, a distal end, and a longitudinal axis. The permeable shell alsoincludes a plurality of elongate resilient filaments with a wovenstructure secured relative to each other at proximal ends and distalends thereof. The permeable shell has a radially constrained elongatedstate configured for delivery within a microcatheter with the thin wovenfilaments extending longitudinally from the proximal end to the distalend radially adjacent each other along a length of the filaments. Thepermeable shell also has an expanded relaxed state with a globular andlongitudinally shortened configuration relative to the radiallyconstrained state with the woven filaments forming the self-expandingresilient permeable shell in a smooth path radially expanded from thelongitudinal axis between the proximal end and distal end including aplurality of openings in the shell formed between the woven filaments,the largest of said openings being configured to allow blood flowthrough the openings at a velocity below a thrombotic thresholdvelocity. The permeable shell may also include a configuration whereinat least the distal end has a reverse bend in an everted recessedconfiguration such that the secured distal ends of the filaments arewithdrawn axially within the nominal contour of the permeable shellstructure in the expanded state.

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell having a proximalend, a distal end, and a longitudinal axis. The permeable shell may alsoinclude a plurality of elongate resilient filaments including largefilaments and small filaments of at least two different transversedimensions with a woven structure secured relative to each other atproximal ends and distal ends thereof. The permeable shell may alsoinclude a radially constrained elongated state configured for deliverywithin a microcatheter with the thin woven filaments extendinglongitudinally from the proximal end to the distal end radially adjacenteach other along a length of the filaments. The permeable shell also hasan expanded relaxed state with a globular and longitudinally shortenedconfiguration relative to the radially constrained state with the wovenfilaments forming the self-expanding resilient permeable shell in asmooth path radially expanded from the longitudinal axis between theproximal end and distal end including a plurality of openings in theshell formed between the woven filaments. The permeable shell may beconfigured such that at least the distal end has a reverse bend in aneverted recessed configuration such that the secured distal ends of thefilaments are withdrawn axially within the nominal permeable shellstructure in the expanded state.

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell having a proximalend, a distal end, and a longitudinal axis. The permeable shell alsoincludes a plurality of elongate resilient filaments including largefilaments and small filaments of different transverse diameters with awoven structure secured relative to each other at proximal ends anddistal ends thereof. The permeable shell may also include a radiallyconstrained elongated state configured for delivery within amicrocatheter with the woven filaments extending longitudinally from theproximal end to the distal end radially adjacent each other along alength of the filaments. The permeable shell also has an expandedrelaxed state with a globular and longitudinally shortened configurationrelative to the radially constrained state with a major transversediameter, the woven filaments forming the self-expanding resilientpermeable shell in a smooth path radially expanded from the longitudinalaxis between the proximal end and distal end, and including a pluralityof openings in the shell formed between the woven filaments. Thepermeable shell may also be configured such that at least the distal endhas a reverse bend in an everted recessed configuration such that thesecured distal ends of the filaments are withdrawn axially within thenominal permeable shell structure in the expanded state. In addition,the permeable shell may have properties such that the diameter of thepermeable shell in an expanded state, number and diameter of largefilaments and number and diameter of small filaments are configured suchthat the permeable shell in an expanded state has a radial stiffness ofabout 0.014 pounds force (lbf) to about 0.284 lbf defined by theexpression (1.2×10⁶ lbf/D⁴)(N_(l)d_(l) ⁴+N_(s)d_(s) ⁴) where D is adiameter of the permeable shell in the expanded state in inches, N_(l)is the number of large filaments in the permeable shell, N_(s) is thenumber of small filaments in the permeable shell, d_(l) is the diameterof the large filaments in inches, and d_(s) is the diameter of the smallfilaments in inches. The equation above contemplates two wire sizes,however, the equation is also applicable to embodiments having one wiresize in which case d_(l) will be equal to d_(s).

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell having a proximalend, a distal end, and a longitudinal axis. The permeable shell also hasa plurality of elongate resilient filaments including large filamentsand small filaments of different transverse diameters with a wovenstructure secured relative to each other at proximal ends and distalends thereof. The permeable shell may also include a radiallyconstrained elongated state configured for delivery within amicrocatheter with the thin woven filaments extending longitudinallyfrom the proximal end to the distal end radially adjacent each otheralong a length of the filaments. The permeable shell has an expandedrelaxed state with a globular and longitudinally shortened configurationrelative to the radially constrained state with a major transversediameter, the woven filaments forming the self-expanding resilientpermeable shell in a smooth path radially expanded from the longitudinalaxis between the proximal end and distal end, and including a pluralityof openings in the shell formed between the woven filaments. Thepermeable shell may also be configured such that at least the distal endhas a reverse bend in an everted recessed configuration such that thesecured distal ends of the filaments are withdrawn axially within thenominal permeable shell structure in the expanded state. The permeableshell may further have properties such that the diameter of thepermeable shell in an expanded state, number of all filaments anddiameter of the small filaments are configured such that the maximumopening size of a portion of the permeable shell in an expanded statethat spans a vascular defect opening or vascular defect neck is lessthan about 0.016 inches with the maximum pore or opening size defined bythe expression (1.7/N_(T))(πD−N_(T)/2d_(w)) where D is a diameter of thepermeable shell in the expanded state in inches, N_(T) is the totalnumber of filaments in the permeable shell, and d_(w) is the diameter ofthe small filaments in inches. The pore size for an opening is definedherein by the largest circular shape that may be disposed within theopening of a braided filament structure.

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell having a proximalend, a distal end, and a longitudinal axis. The permeable shell furtherincludes a plurality of elongate resilient filaments including largefilaments and small filaments of different transverse diameters with awoven structure secured relative to each other at proximal ends anddistal ends thereof. The permeable shell may also have a radiallyconstrained elongated state configured for delivery within amicrocatheter with the woven filaments extending longitudinally from theproximal end to the distal end radially adjacent each other along alength of the filaments. The permeable shell also includes an expandedrelaxed state with a globular and longitudinally shortened configurationrelative to the radially constrained state with a major transversediameter, the woven filaments forming the self-expanding resilientpermeable shell in a smooth path radially expanded from the longitudinalaxis between the proximal end and distal end, and including a pluralityof openings in the shell formed between the woven filaments. Thepermeable shell may also be configured such that at least the distal endhas a reverse bend in an everted recessed configuration such that thesecured distal ends of the filaments are withdrawn axially within thenominal permeable shell structure in the expanded state. The permeableshell may also have properties such that the diameter of the permeableshell in an expanded state, number and diameter of large filaments andnumber and diameter of small filaments are configured such that thepermeable shell in a constrained state has an outer transverse diameterof less than about 0.04 inches defined by the expression1.48((N_(l)d_(l) ²+N_(s)d_(s) ²))^(1/2) where N_(l) is the number oflarge filaments in the permeable shell, N_(s) is the number of smallfilaments in the permeable shell, d_(l) is the diameter of the largefilaments in inches, and d_(s) is the diameter of the small filaments ininches.

Some embodiments of a method of treating a vascular defect of a patientinclude providing a device for treatment of a patient's vasculaturecomprising a self-expanding resilient permeable shell of wovenfilaments, the permeable shell having a proximal end, a distal end, alongitudinal axis, a radially constrained elongated state configured fordelivery within a microcatheter with the woven filaments extendinglongitudinally from the proximal end to the distal radially adjacenteach other. The permeable shell may also have an expanded relaxed statewith a globular and axially shortened configuration relative to theconstrained state with the woven filaments forming the self-expandingresilient permeable shell in a smooth path radially expanded from thelongitudinal axis between the proximal end and distal end with the shellhaving a reverse bend at each end in an everted recessed configurationsuch that a hub at the distal end is withdrawn axially within thepermeable shell structure. The permeable shell also has and a pluralityof openings in the shell formed between the woven filaments. Onceprovided, a delivery system is advanced within a patient's body suchthat a distal end of the delivery system is disposed at a positionadjacent or within a vascular defect to be treated. The device is thenaxially advanced within the delivery system while in a radiallyconstrained state with an elongate delivery apparatus which has a distalend releasably secured to a proximal end of the device. The device isfurther advanced distally until the device emerges from a distal end ofthe delivery system. The device is further advanced from the distal endof the delivery system until it is deployed such that the wovenfilaments of the device radially expand from their radially constrainedstate, and expand into a globular configuration of the permeable shell.The deployed device then covers and acutely occludes at least a portionof an opening or neck of the vascular defect due to the pore size of thepermeable shell which slows a flow of blood therethrough to a velocitybelow a thrombotic threshold velocity.

Some embodiments of a method of treating a cerebral aneurysm within acerebral vasculature of a patient include providing a microcatheterhaving a proximal end, a distal end, and a lumen therebetween. Thedevice for treatment of an aneurysm within a patient's vasculatureincludes a self-expanding resilient permeable shell having a proximalend, a distal end, and a longitudinal axis. The device includes aplurality of elongate resilient filaments with a woven structure,wherein the plurality of filaments includes small filaments and largefilaments, wherein the small filaments have a transverse dimensionsmaller than the transverse dimension of the large filaments, the wovenstructure having a radially constrained elongated state configured fordelivery within a microcatheter with the thin woven filaments extendinglongitudinally from the proximal end to the distal end radially adjacenteach other along a length of the filaments, wherein the filaments arebundled and secured to each other at a proximal end, wherein a ratio ofthe total cross-sectional area of small filaments to the totalcross-sectional area of large filaments is between 0.56 and 1.89. Thedistal end of the microcatheter may be advanced to a region of interestwithin a cerebral artery. The device may be advanced through the lumenand out of the distal end of the microcatheter such that the permeableshell deploys within the cerebral aneurysm, wherein the permeable shellexpands to an expanded state within the cerebral aneurysm, the expandedrelaxed state having a longitudinally shortened configuration relativeto the radially constrained state. The microcatheter may be withdrawnfrom the cerebral artery, wherein the permeable shell is the onlyimplant delivered into the cerebral aneurysm through the microcatheterbefore the microcatheter is withdrawn.

Some methods of occluding a vascular defect of a patient's vasculatureinclude providing an expandable, porous vascular occlusion device formedfrom a woven shell of a plurality of filamentary members that areconnected to each other on at least the proximal ends of the membersforming a substantially closed globular structure with a shape thatapproximates or is slightly larger than a size and shape of the vasculardefect and wherein the distal ends of the filamentary members arerecessed within a nominal surface contour of the globular structure ofthe device. Once the device is provided, the device may be collapsed fordelivery into the vascular system of the patient. The collapsed devicemay then be inserted through an incision in the patient's body and thedevice released and expanded at the vascular defect such that an outersurface contour of the device substantially fills the vascular defect.The device then substantially occludes the vascular defect acutely andbecomes substantially covered with clotted blood.

Some embodiments of a delivery system for deployment of a device fortreatment of a patient's vasculature include a microcatheter having aninner lumen extending a length thereof and a device for treatment of apatient's vasculature disposed within the inner lumen of themicrocatheter. The device also includes a self-expanding resilientpermeable shell of thin coupled filaments, the permeable shell having aproximal end, a distal end, a longitudinal axis, a radially constrainedelongated state configured for delivery within a microcatheter with thethin woven filaments extending longitudinally from the proximal end tothe distal radially adjacent each other. The permeable shell also has anexpanded relaxed state with a globular and axially shortenedconfiguration relative to the constrained state with the woven filamentsforming the self-expanding resilient permeable shell in a smooth pathradially expanded from the longitudinal axis between the proximal endand distal end. The permeable shell may further include a reverse bendat each end in an everted recessed configuration such that a hub at thedistal end is disposed axially within the permeable shell structure. Thepermeable shell also has a plurality of openings formed between thewoven filaments, the permeable shell further having a portion when inthe expanded relaxed state that is configured to span an opening of apatient's vascular defect. The delivery system further includes anelongate delivery apparatus having a proximal end and a distal endreleasably secured to a proximal hub of the device.

Some embodiments of a method of manufacturing a device for treatment ofa patient's vasculature include braiding a plurality of elongateresilient filaments over a cylindrically shaped mandrel forming abraided tubular member. The elongate filaments of the braided tubularmember may then be heat set in an expanded relaxed state with a globularand axially shortened configuration relative to a constrained state withthe woven filaments forming the self-expanding resilient permeable shellin a smooth path radially expanded from a longitudinal axis of thedevice between a proximal end and a distal end of the device with theshell having a reverse bend at the distal end in an everted recessedconfiguration such that a hub at the distal end is withdrawn disposedwithin the permeable shell structure and a plurality of openings in theshell are formed between the woven filaments. The proximal ends of thefilaments are then secured together and the distal ends of the filamentsare secured together.

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell of thininterconnected filaments that serves as a support structure and integraldefect spanning structure, the permeable shell having a first end, asecond end, a longitudinal axis, a constrained cylindrical stateconfigured for delivery within a microcatheter with the thininterconnected filaments extending from the first end to the second end.The permeable shell also has an expanded relaxed state with a globularand axially shortened configuration relative to the constrained statewith filaments forming a smooth arc between the first end and second endwith a reverse bend at each end in an everted recessed configuration.The permeable shell further has a defect spanning portion when in theexpanded relaxed state that is configured to span an opening of apatient's vascular defect.

Some embodiments of a method of treating a vascular defect includeproviding a device for treatment of a patient's vasculature having aself-expanding resilient permeable shell of thin interconnectedfilaments that serves as a support structure and integral defectspanning structure. The permeable shell also has a first end, a secondend, a longitudinal axis, a constrained cylindrical state configured fordelivery within a microcatheter with the thin interconnected filamentsextending from the first end to the second end. The permeable shell alsohas an expanded relaxed state with a globular and axially shortenedconfiguration relative to the constrained state with filaments forming asmooth arc between the first end and second end with a reverse bend ateach end in an everted recessed configuration. The permeable shellfurther has a defect spanning portion when in the expanded relaxed statethat is configured to span an opening of a patient's vascular defect.Once provided, the delivery system may be advanced to a positionadjacent a vascular defect to be treated and positioned with a distalend disposed inside the vascular defect. The device may then be deployedsuch that the permeable shell self-expands and the defect spanningportion of the permeable shell covers at least a portion of the defectopening or neck.

Some embodiments of a device for treatment of a patient's vasculatureinclude a self-expanding resilient permeable shell of thininterconnected filaments that serves as a support structure and integraldefect spanning structure. The permeable shell also has a first end, asecond end, a longitudinal axis, a constrained cylindrical stateconfigured for delivery within a microcatheter with the thininterconnected filaments extending from the first end to the second end.The permeable shell also has an expanded relaxed state with a globularand axially shortened configuration relative to the constrained statewith filaments forming a smooth arc between the first end and second endwith a reverse bend at each end in an everted recessed configuration.The permeable shell further includes a defect spanning portion when inthe expanded relaxed state that is configured to span an opening of apatient's vascular defect.

Some embodiments of a method of treating a vascular defect includeproviding a device for treatment of a patient's vasculature having aself-expanding resilient permeable shell of thin interconnectedfilaments that serves as a support structure and integral defectspanning structure. The permeable shell also has a first end, a secondend, a longitudinal axis, a constrained cylindrical state configured fordelivery within a microcatheter with the thin interconnected filamentsextending from the first end to the second end. The permeable shellfurther includes an expanded relaxed state with a globular and axiallyshortened configuration relative to the constrained state with filamentsforming a smooth arc between the first end and second end with a reversebend at each end in an everted recessed configuration. The permeableshell also has a defect spanning portion when in the expanded relaxedstate that is configured to span an opening of a patient's vasculardefect. Once the device has been provided, a delivery system may beadvanced to a position adjacent a vascular defect to be treated. Thedevice is then positioned inside the vascular defect and deployed suchthat the permeable shell self-expands and the defect spanning portion ofthe permeable shell covers at least a portion of the defect opening orneck.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an elevation view of an embodiment of a device for treatmentof a patient's vasculature and a plurality of arrows indicating inwardradial force.

FIG. 2 is an elevation view of a beam supported by two simple supportsand a plurality of arrows indicating force against the beam.

FIG. 3 is a bottom perspective view of an embodiment of a device fortreatment of a patient's vasculature.

FIG. 4 is an elevation view of the device for treatment of a patient'svasculature of FIG. 3.

FIG. 5 is a transverse cross sectional view of the device of FIG. 4taken along lines 5-5 in FIG. 4.

FIG. 6 shows the device of FIG. 4 in longitudinal section taken alonglines 6-6 in FIG. 4.

FIG. 7 is an enlarged view of the woven filament structure taken fromthe encircled portion 7 shown in FIG. 5.

FIG. 8 is an enlarged view of the woven filament structure taken fromthe encircled portion 8 shown in FIG. 6.

FIG. 9 is a proximal end view of the device of FIG. 3.

FIG. 10 is a transverse sectional view of a proximal hub portion of thedevice in FIG. 6 indicated by lines 10-10 in FIG. 6.

FIG. 11 is an elevation view in partial section of a distal end of adelivery catheter with the device for treatment of a patient'svasculature of FIG. 3 disposed therein in a collapsed constrained state.

FIG. 12 is an elevation view of a distal portion of a delivery device oractuator showing some internal structure of the device.

FIG. 13 is an elevation view of the delivery device of FIG. 12 with theaddition of some tubular elements over the internal structures.

FIG. 14 is an elevation view of the distal portion of the deliverydevice of FIG. 13 with an outer coil and marker in place.

FIG. 15 is an elevation view of a proximal portion of the deliverydevice.

FIG. 16 illustrates an embodiment of a filament configuration for adevice for treatment of a patient's vasculature.

FIG. 17 is a schematic view of a patient being accessed by an introducersheath, a microcatheter and a device for treatment of a patient'svasculature releasably secured to a distal end of a delivery device oractuator.

FIG. 18 is a sectional view of a terminal aneurysm.

FIG. 19 is a sectional view of an aneurysm.

FIG. 20 is a schematic view in section of an aneurysm showingperpendicular arrows which indicate interior nominal longitudinal andtransverse dimensions of the aneurysm.

FIG. 21 is a schematic view in section of the aneurysm of FIG. 20 with adashed outline of a device for treatment of a patient's vasculature in arelaxed unconstrained state that extends transversely outside of thewalls of the aneurysm.

FIG. 22 is a schematic view in section of an outline of a devicerepresented by the dashed line in FIG. 21 in a deployed and partiallyconstrained state within the aneurysm.

FIGS. 23-26 show a deployment sequence of a device for treatment of apatient's vasculature.

FIG. 27 is an elevation view in partial section of an embodiment of adevice for treatment of a patient's vasculature deployed within ananeurysm at a tilted angle.

FIG. 28 is an elevation view in partial section of an embodiment of adevice for treatment of a patient's vasculature deployed within anirregularly shaped aneurysm.

FIG. 29 shows an elevation view in section of a device for treatment ofa patient's vasculature deployed within a vascular defect aneurysm.

FIG. 30 shows a proximal perspective view of an embodiment of a devicefor treatment of a patient's vasculature with a sealing zone embodimentindicated by a set of dashed lines.

FIGS. 31-35 illustrate various different embodiments of braidingpatterns that may be used for permeable shells of devices for treatmentof a patient's vasculature.

FIG. 36 illustrates a device for treatment of a patient's vasculaturethat includes non-structural fibers in the permeable shell structure ofthe device.

FIG. 37 is an enlarged view of non-structural fibers woven intofilaments of a permeable shell structure.

FIG. 38 is an elevation view of a mandrel used for manufacture of abraided tubular member for construction of an embodiment of a device fortreatment of a patient's vasculature with the initiation of the braidingprocess shown.

FIG. 39 is an elevation view of a braiding process for a braided tubularmember used for manufacture of a device.

FIG. 40 is an elevation view in partial section of an embodiment of afixture for heat setting a braided tubular member for manufacture of adevice for treatment of a patient's vasculature.

FIG. 41 is an elevation view in partial section of an embodiment of afixture for heat setting a braided tubular member for manufacture of adevice for treatment of a patient's vasculature.

FIG. 42 is an elevation view in section of a device for treatment of apatient's vasculature.

FIG. 43 is a transverse sectional view of the device in FIG. 42indicated by lines 7-7 in FIG. 42.

FIGS. 43A-E illustrate various embodiments of filament configurationsfor the device for treatment of a patient's vasculature.

DETAILED DESCRIPTION

Discussed herein are devices and methods for the treatment of vasculardefects that are suitable for minimally invasive deployment within apatient's vasculature, and particularly, within the cerebral vasculatureof a patient. For such embodiments to be safely and effectivelydelivered to a desired treatment site and effectively deployed, somedevice embodiments may be configured for collapse to a low profileconstrained state with a transverse dimension suitable for deliverythrough an inner lumen of a microcatheter and deployment from a distalend thereof. Embodiments of these devices may also maintain a clinicallyeffective configuration with sufficient mechanical integrity oncedeployed so as to withstand dynamic forces within a patient'svasculature over time that may otherwise result in compaction of adeployed device. It may also be desirable for some device embodiments toacutely occlude a vascular defect of a patient during the course of aprocedure in order to provide more immediate feedback regarding successof the treatment to a treating physician.

Some embodiments are particularly useful for the treatment of cerebralaneurysms by reconstructing a vascular wall so as to wholly or partiallyisolate a vascular defect from a patient's blood flow. Some embodimentsmay be configured to be deployed within a vascular defect to facilitatereconstruction, bridging of a vessel wall or both in order to treat thevascular defect. For some of these embodiments, the permeable shell ofthe device may be configured to anchor or fix the permeable shell in aclinically beneficial position. For some embodiments, the device may bedisposed in whole or in part within the vascular defect in order toanchor or fix the device with respect to the vascular structure ordefect. The permeable shell may be configured to span an opening, neckor other portion of a vascular defect in order to isolate the vasculardefect, or a portion thereof, from the patient's nominal vascular systemin order allow the defect to heal or to otherwise minimize the risk ofthe defect to the patient's health.

For some or all of the embodiments of devices for treatment of apatient's vasculature discussed herein, the permeable shell may beconfigured to allow some initial perfusion of blood through thepermeable shell. The porosity of the permeable shell may be configuredto sufficiently isolate the vascular defect so as to promote healing andisolation of the defect, but allow sufficient initial flow through thepermeable shell so as to reduce or otherwise minimize the mechanicalforce exerted on the membrane the dynamic flow of blood or other fluidswithin the vasculature against the device. For some embodiments ofdevices for treatment of a patient's vasculature, only a portion of thepermeable shell that spans the opening or neck of the vascular defect,sometimes referred to as a defect spanning portion, need be permeableand/or conducive to thrombus formation in a patient's bloodstream. Forsuch embodiments, that portion of the device that does not span anopening or neck of the vascular defect may be substantiallynon-permeable or completely permeable with a pore or openingconfiguration that is too large to effectively promote thrombusformation.

In general, it may be desirable in some cases to use a hollow, thinwalled device with a permeable shell of resilient material that may beconstrained to a low profile for delivery within a patient. Such adevice may also be configured to expand radially outward upon removal ofthe constraint such that the shell of the device assumes a larger volumeand fills or otherwise occludes a vascular defect within which it isdeployed. The outward radial expansion of the shell may serve to engagesome or all of an inner surface of the vascular defect wherebymechanical friction between an outer surface of the permeable shell ofthe device and the inside surface of the vascular defect effectivelyanchors the device within the vascular defect. Some embodiments of sucha device may also be partially or wholly mechanically captured within acavity of a vascular defect, particularly where the defect has a narrowneck portion with a larger interior volume. In order to achieve a lowprofile and volume for delivery and be capable of a high ratio ofexpansion by volume, some device embodiments include a matrix of wovenor braided filaments that are coupled together by the interwovenstructure so as to form a self-expanding permeable shell having a poreor opening pattern between couplings or intersections of the filamentsthat is substantially regularly spaced and stable, while still allowingfor conformity and volumetric constraint.

As used herein, the terms woven and braided are used interchangeably tomean any form of interlacing of filaments to form a mesh structure. Inthe textile and other industries, these terms may have different or morespecific meanings depending on the product or application such aswhether an article is made in a sheet or cylindrical form. For purposesof the present disclosure, these terms are used interchangeably.

For some embodiments, three factors may be critical for a woven orbraided wire occlusion device for treatment of a patient's vasculaturethat can achieve a desired clinical outcome in the endovasculartreatment of cerebral aneurysms. We have found that for effective use insome applications, it may be desirable for the implant device to havesufficient radial stiffness for stability, limited pore size fornear-complete acute (intra-procedural) occlusion and a collapsed profilewhich is small enough to allow insertion through an inner lumen of amicrocatheter. A device with a radial stiffness below a certainthreshold may be unstable and may be at higher risk of embolization insome cases. Larger pores between filament intersections in a braided orwoven structure may not generate thrombus and occlude a vascular defectin an acute setting and thus may not give a treating physician or healthprofessional such clinical feedback that the flow disruption will leadto a complete and lasting occlusion of the vascular defect beingtreated. Delivery of a device for treatment of a patient's vasculaturethrough a standard microcatheter may be highly desirable to allow accessthrough the tortuous cerebral vasculature in the manner that a treatingphysician is accustomed.

For some embodiments, it may be desirable to use filaments having two ormore different diameters or transverse dimensions to form a permeableshell in order to produce a desired configuration as discussed in moredetail below. The radial stiffness of a two-filament (two differentdiameters) woven device may be expressed as a function of the number offilaments and their diameters, as follows:S _(radial)=(1.2×10⁶ lbf/D ⁴)(N _(l) d _(l) ⁴ +N _(s) d _(s) ⁴)where

-   -   S_(radial) is the radial stiffness in pounds force (lbf),    -   D is the Device diameter (transverse dimension),    -   N_(l) is the number of large filaments,    -   N_(s) is the number of small filaments,    -   d_(l) is the diameter of the large filaments in inches, and    -   d_(s) is the diameter of the small filaments in inches.

Using this expression, the radial stiffness, S_(radial) may be betweenabout 0.014 and 0.284 lbf force for some embodiments of particularclinical value.

The maximum pore size in a portion of a device that spans a neck oropening of a vascular defect desirable for some useful embodiments of awoven wire device for treatment of a patient's vasculature may beexpressed as a function of the total number of all filaments, filamentdiameter and the device diameter. The difference between filament sizeswhere two or more filament diameters or transverse dimensions are usedmay be ignored in some cases for devices where the filament size(s) arevery small compared to the device dimensions. For a two-filament device,the smallest filament diameter may be used for the calculation. Thus,the maximum pore size for such embodiments may be expressed as follows:P _(max)=(1.7/N _(T))(πD−(N _(T) d _(w)/2))

where P_(max) is the average pore size,

D is the Device diameter (transverse dimension),

N_(T) is the total number of all filaments, and

d_(w) is the diameter of the filaments (smallest) in inches.

Using this expression, the maximum pore size, P_(max), of a portion of adevice that spans an opening of a vascular defect or neck, or any othersuitable portion of a device, may be less than about 0.016 inches orabout 400 microns for some embodiments. In some embodiments the maximumpore size for a defect spanning portion or any other suitable portion ofa device may be less than about 0.012 inches or about 300 microns.

The collapsed profile of a two-filament (profile having two differentfilament diameters) woven filament device may be expressed as thefunction:P _(c)=1.48((N _(l) d _(l) ² +N _(s) d _(s) ²))^(1/2)

where P_(c) is the collapsed profile of the device,

N_(l) is the number of large filaments,

N_(s) is the number of small filaments,

d_(l) is the diameter of the large filaments in inches, and

d_(s) is the diameter of the small filaments in inches.

Using this expression, the collapsed profile P_(c) may be less thanabout 1.0 mm for some embodiments of particular clinical value.

In some embodiments of particular clinical value, the device may beconstructed so as to have all three factors (S_(radial), P_(max) andP_(c)) above within the ranges discussed above; S_(radial) between about0.014 lbf and 0.284 lbf, P_(max) less than about 300 microns and P_(c)less than about 1.0 mm, simultaneously. In some such embodiments, thedevice may be made to include about 70 filaments to about 300 filaments.In some cases, the filaments may have an outer transverse dimension ordiameter of about 0.0004 inches to about 0.002 inches.

As has been discussed, some embodiments of devices for treatment of apatient's vasculature call for sizing the device which approximates (orwith some over-sizing) the vascular site dimensions to fill the vascularsite. One might assume that scaling of a device to larger dimensions andusing larger filaments would suffice for such larger embodiments of adevice. However, for the treatment of brain aneurysms, the diameter orprofile of the radially collapsed device is limited by the cathetersizes that can be effectively navigated within the small, tortuousvessels of the brain. Further, as a device is made larger with a givenor fixed number of resilient filaments having a given size or thickness,the pores or openings between junctions of the filaments arecorrespondingly larger. In addition, for a given filament size theflexural modulus or stiffness of the filaments and thus the structuredecrease with increasing device dimension. Flexural modulus may bedefined as the ratio of stress to strain. Thus, a device may beconsidered to have a high flexural modulus or be stiff if the strain(deflection) is low under a given force. A stiff device may also said tohave low compliance.

To properly configure larger size devices for treatment of a patient'svasculature, it may be useful to model the force on a device when thedevice is deployed into a vascular site or defect, such as a bloodvessel or aneurysm, that has a diameter or transverse dimension that issmaller than a nominal diameter or transverse dimension of the device ina relaxed unconstrained state. As discussed, it may be advisable to“over-size” the device in some cases so that there is a residual forcebetween an outside surface of the device and an inside surface of thevascular wall. The inward radial force on a device 10 that results fromover-sizing is illustrated schematically in FIG. 1 with the arrows 12 inthe figure representing the inward radial force. As shown in FIG. 2,these compressive forces on the filaments 14 of the device in FIG. 1 canbe modeled as a simply supported beam 16 with a distributed load orforce as show by the arrows 18 in the figure. It can be seen from theequation below for the deflection of a beam with two simple supports 20and a distributed load that the deflection is a function of the length,L to the 4^(th) power:Deflection of Beam=5FL ⁴/384 EI

-   -   where F=force,    -   L=length of beam,    -   E=Young's Modulus, and    -   I=moment of inertia.

Thus, as the size of the device increases and L increases, thecompliance increases substantially. Accordingly, an outward radial forceexerted by an outside surface of the filaments 14 of the device 10against a constraining force when inserted into a vascular site such asblood vessel or aneurysm is lower for a given amount of devicecompression or over-sizing. This force may be important in someapplications to assure device stability and to reduce the risk ofmigration of the device and potential distal embolization.

In some embodiments, a combination of small and large filament sizes maybe utilized to make a device with a desired radial compliance and yethave a collapsed profile which is configured to fit through an innerlumen of commonly used microcatheters. A device fabricated with even asmall number of relatively large filaments 14 can provide reduced radialcompliance (or increased stiffness) compared to a device made with allsmall filaments. Even a relatively small number of larger filaments mayprovide a substantial increase in bending stiffness due to change in themoment of Inertia that results from an increase in diameter withoutincreasing the total cross sectional area of the filaments. The momentof inertia (I) of a round wire or filament may be defined by theequation:I=πd ⁴/64

-   -   where d is the diameter of the wire or filament.

Since the moment of inertia is a function of filament diameter to thefourth power, a small change in the diameter greatly increases themoment of inertia. Thus, a small change in filament size can havesubstantial impact on the deflection at a given load and thus thecompliance of the device.

Thus, the stiffness can be increased by a significant amount without alarge increase in the cross sectional area of a collapsed profile of thedevice 10. This may be particularly important as device embodiments aremade larger to treat large aneurysms. While large cerebral aneurysms maybe relatively rare, they present an important therapeutic challenge assome embolic devices currently available to physicians have relativelypoor results compared to smaller aneurysms.

As such, some embodiments of devices for treatment of a patient'svasculature may be formed using a combination of filaments 14 with anumber of different diameters such as 2, 3, 4, 5 or more differentdiameters or transverse dimensions. In device embodiments wherefilaments with two different diameters are used, some larger filamentembodiments may have a transverse dimension of about 0.001 inches toabout 0.004 inches and some small filament embodiments may have atransverse dimension or diameter of about 0.0004 inches and about 0.0015inches, more specifically, about 0.0004 inches to about 0.001 inches.The ratio of the number of large filaments to the number of smallfilaments may be between about 2 and 12 and may also be between about 4and 8. In some embodiments, the difference in diameter or transversedimension between the larger and smaller filaments may be less thanabout 0.004 inches, more specifically, less than about 0.0035 inches,and even more specifically, less than about 0.002 inches.

As discussed above, device embodiments 10 for treatment of a patient'svasculature may include a plurality of wires, fibers, threads, tubes orother filamentary elements that form a structure that serves as apermeable shell. For some embodiments, a globular shape may be formedfrom such filaments by connecting or securing the ends of a tubularbraided structure. For such embodiments, the density of a braided orwoven structure may inherently increase at or near the ends where thewires or filaments 14 are brought together and decrease at or near amiddle portion 30 disposed between a proximal end 32 and distal end 34of the permeable shell 40. For some embodiments, an end or any othersuitable portion of a permeable shell 40 may be positioned in an openingor neck of a vascular defect such as an aneurysm for treatment. As such,a braided or woven filamentary device with a permeable shell may notrequire the addition of a separate defect spanning structure havingproperties different from that of a nominal portion of the permeableshell to achieve hemostasis and occlusion of the vascular defect. Such afilamentary device may be fabricated by braiding, weaving or othersuitable filament fabrication techniques. Such device embodiments may beshape set into a variety of three dimensional shapes such as discussedherein.

Referring to FIGS. 3-10, an embodiment of a device for treatment of apatient's vasculature 10 is shown. The device 10 includes aself-expanding resilient permeable shell 40 having a proximal end 32, adistal end 34, a longitudinal axis 46 and further comprising a pluralityof elongate resilient filaments 14 including large filaments 48 andsmall filaments 50 of at least two different transverse dimensions asshown in more detail in FIGS. 5,7 and 18. The filaments 14 have a wovenstructure and are secured relative to each other at proximal ends 60 anddistal ends 62 thereof. The permeable shell 40 of the device has aradially constrained elongated state configured for delivery within amicrocatheter 61, as shown in FIG. 11, with the thin woven filaments 14extending longitudinally from the proximal end 42 to the distal end 44radially adjacent each other along a length of the filaments.

As shown in FIGS. 3-6, the permeable shell 40 also has an expandedrelaxed state with a globular and longitudinally shortened configurationrelative to the radially constrained state. In the expanded state, thewoven filaments 14 form the self-expanding resilient permeable shell 40in a smooth path radially expanded from a longitudinal axis 46 of thedevice between the proximal end 32 and distal end 34. The wovenstructure of the filaments 14 includes a plurality of openings 64 in thepermeable shell 40 formed between the woven filaments. For someembodiments, the largest of said openings 64 may be configured to allowblood flow through the openings only at a velocity below a thromboticthreshold velocity. Thrombotic threshold velocity has been defined, atleast by some, as the time-average velocity at which more than 50% of avascular graft surface is covered by thrombus when deployed within apatient's vasculature. In the context of aneurysm occlusion, a slightlydifferent threshold may be appropriate. Accordingly, the thromboticthreshold velocity as used herein shall include the velocity at whichclotting occurs within or on a device, such as device 10, deployedwithin a patient's vasculature such that blood flow into a vasculardefect treated by the device is substantially blocked in less than about1 hour or otherwise during the treatment procedure. The blockage ofblood flow into the vascular defect may be indicated in some cases byminimal contrast agent entering the vascular defect after a sufficientamount of contrast agent has been injected into the patient'svasculature upstream of the implant site and visualized as it dissipatesfrom that site. Such sustained blockage of flow within less than about 1hour or during the duration of the implantation procedure may also bereferred to as acute occlusion of the vascular defect.

As such, once the device 10 is deployed, any blood flowing through thepermeable shell may be slowed to a velocity below the thromboticthreshold velocity and thrombus will begin to form on and around theopenings in the permeable shell 40. Ultimately, this process may beconfigured to produce acute occlusion of the vascular defect withinwhich the device 10 is deployed. For some embodiments, at least thedistal end of the permeable shell 40 may have a reverse bend in aneverted configuration such that the secured distal ends 62 of thefilaments 14 are withdrawn axially within the nominal permeable shellstructure or contour in the expanded state. For some embodiments, theproximal end of the permeable shell further includes a reverse bend inan everted configuration such that the secured proximal ends 60 of thefilaments 14 are withdrawn axially within the nominal permeable shellstructure 40 in the expanded state. As used herein, the term everted mayinclude a structure that is everted, partially everted and/or recessedwith a reverse bend as shown in the device embodiment of FIGS. 3-6. Forsuch embodiments, the ends 60 and 62 of the filaments 14 of thepermeable shell or hub structure disposed around the ends may bewithdrawn within or below the globular shaped periphery of the permeableshell of the device.

The elongate resilient filaments 14 of the permeable shell 40 may besecured relative to each other at proximal ends 60 and distal ends 62thereof by one or more methods including welding, soldering, adhesivebonding, epoxy bonding or the like. In addition to the ends of thefilaments being secured together, a distal hub 66 may also be secured tothe distal ends 62 of the thin filaments 14 of the permeable shell 40and a proximal hub 68 secured to the proximal ends 60 of the thinfilaments 14 of the permeable shell 40. The proximal hub 68 may includea cylindrical member that extends proximally beyond the proximal ends 60of the thin filaments so as to form a cavity 70 within a proximalportion of the proximal hub 68. The proximal cavity 70 may be used forholding adhesives such as epoxy, solder or any other suitable bondingagent for securing an elongate detachment tether 72 that may in turn bedetachably secured to a delivery apparatus such as is shown in FIGS.11-15.

For some embodiments, the elongate resilient filaments 14 of thepermeable shell 40 may have a transverse cross section that issubstantially round in shape and be made from a superelastic materialthat may also be a shape memory metal. The shape memory metal of thefilaments of the permeable shell 40 may be heat set in the globularconfiguration of the relaxed expanded state as shown in FIGS. 3-6.Suitable superelastic shape memory metals may include alloys such asNiTi alloy and the like. The superelastic properties of such alloys maybe useful in providing the resilient properties to the elongatefilaments 14 so that they can be heat set in the globular form shown,fully constrained for delivery within an inner lumen of a microcatheterand then released to self expand back to substantially the original heatset shape of the globular configuration upon deployment within apatient's body.

The device 10 may have an everted filamentary structure with a permeableshell 40 having a proximal end 32 and a distal end 34 in an expandedrelaxed state. The permeable shell 40 has a substantially enclosedconfiguration for the embodiments shown. Some or all of the permeableshell 40 of the device 10 may be configured to substantially block orimpede fluid flow or pressure into a vascular defect or otherwiseisolate the vascular defect over some period of time after the device isdeployed in an expanded state. The permeable shell 40 and device 10generally also has a low profile, radially constrained state, as shownin FIG. 11, with an elongated tubular or cylindrical configuration thatincludes the proximal end 32, the distal end 34 and a longitudinal axis46. While in the radially constrained state, the elongate flexiblefilaments 14 of the permeable shell 40 may be disposed substantiallyparallel and in close lateral proximity to each other between theproximal end and distal end forming a substantially tubular orcompressed cylindrical configuration.

Proximal ends 60 of at least some of the filaments 14 of the permeableshell 40 may be secured to the proximal hub 68 and distal ends 62 of atleast some of the filaments 14 of the permeable shell 40 are secured tothe distal hub 66, with the proximal hub 68 and distal hub 66 beingdisposed substantially concentric to the longitudinal axis 46 as shownin FIG. 4. The ends of the filaments 14 may be secured to the respectivehubs 66 and 68 by any of the methods discussed above with respect tosecurement of the filament ends to each other, including the use ofadhesives, solder, welding and the like. A middle portion 30 of thepermeable shell 40 may have a first transverse dimension with a lowprofile suitable for delivery from a microcatheter as shown in FIG. 11.Radial constraint on the device 10 may be applied by an inside surfaceof the inner lumen of a microcatheter, such as the distal end portion ofthe microcatheter 61 shown, or it may be applied by any other suitablemechanism that may be released in a controllable manner upon ejection ofthe device 10 from the distal end of the catheter. In FIG. 11 a proximalend or hub 68 of the device 10 is secured to a distal end of an elongatedelivery apparatus 110 of a delivery system 112 disposed at the proximalhub 68 of the device 10.

Some device embodiments 10 having a braided or woven filamentarystructure may be formed using about 10 filaments to about 300 filaments14, more specifically, about 10 filaments to about 100 filaments 14, andeven more specifically, about 60 filaments to about 80 filaments 14.Some embodiments of a permeable shell 40 may include about 70 filamentsto about 300 filaments extending from the proximal end 32 to the distalend 34, more specifically, about 100 filaments to about 200 filamentsextending from the proximal end 32 to the distal end 34. For someembodiments, the filaments 14 may have a transverse dimension ordiameter of about 0.0008 inches to about 0.004 inches. The elongateresilient filaments 14 in some cases may have an outer transversedimension or diameter of about 0.0005 inch to about 0.005 inch, morespecifically, about 0.001 inch to about 0.003 inch, and in some casesabout 0.0004 inches to about 0.002 inches. For some device embodiments10 that include filaments 14 of different sizes, the large filaments 48of the permeable shell 40 may have a transverse dimension or diameterthat is about 0.001 inches to about 0.004 inches and the small filaments50 may have a transverse dimension or diameter of about 0.0004 inches toabout 0.0015 inches, more specifically, about 0.0004 inches to about0.001 inches. In addition, a difference in transverse dimension ordiameter between the small filaments 50 and the large filaments 48 maybe less than about 0.004 inches, more specifically, less than about0.0035 inches, and even more specifically, less than about 0.002 inches.For embodiments of permeable shells 40 that include filaments 14 ofdifferent sizes, the number of small filaments 50 of the permeable shell40 relative to the number of large filaments 48 of the permeable shell40 may be about 2 to 1 to about 15 to 1, more specifically, about 2 to 1to about 12 to 1, and even more specifically, about 4 to 1 to about 8 to1.

The expanded relaxed state of the permeable shell 40, as shown in FIG.4, has an axially shortened configuration relative to the constrainedstate such that the proximal hub 68 is disposed closer to the distal hub66 than in the constrained state. Both hubs 66 and 68 are disposedsubstantially concentric to the longitudinal axis 46 of the device andeach filamentary element 14 forms a smooth arc between the proximal anddistal hubs 66 and 68 with a reverse bend at each end. A longitudinalspacing between the proximal and distal hubs 66 and 68 of the permeableshell 40 in a deployed relaxed state may be about 25 percent to about 75percent of the longitudinal spacing between the proximal and distal hubs66 and 68 in the constrained cylindrical state, for some embodiments.The arc of the filaments 14 between the proximal and distal ends 32 and34 may be configured such that a middle portion of each filament 14 hasa second transverse dimension substantially greater than the firsttransverse dimension.

For some embodiments, the permeable shell 40 may have a first transversedimension in a collapsed radially constrained state of about 0.2 mm toabout 2 mm and a second transverse dimension in a relaxed expanded stateof about 4 mm to about 30 mm. For some embodiments, the secondtransverse dimension of the permeable shell 40 in an expanded state maybe about 2 times to about 150 times the first transverse dimension, morespecifically, about 10 times to about 25 times the first or constrainedtransverse dimension. A longitudinal spacing between the proximal end 32and distal end 34 of the permeable shell 40 in the relaxed expandedstate may be about 25% percent to about 75% percent of the spacingbetween the proximal end 32 and distal end 34 in the constrainedcylindrical state. For some embodiments, a major transverse dimension ofthe permeable shell 40 in a relaxed expanded state may be about 4 mm toabout 30 mm, more specifically, about 9 mm to about 15 mm, and even morespecifically, about 4 mm to about 8 mm.

An arced portion of the filaments 14 of the permeable shell 40 may havea sinusoidal-like shape with a first or outer radius 88 and a second orinner radius 90 near the ends of the permeable shell 40 as shown in FIG.6. This sinusoid-like or multiple curve shape may provide a concavity inthe proximal end 32 that may reduce an obstruction of flow in a parentvessel adjacent a vascular defect. For some embodiments, the firstradius 88 and second radius 90 of the permeable shell 40 may be betweenabout 0.12 mm to about 3 mm. For some embodiments, the distance betweenthe proximal end 32 and distal end 34 may be less than about 60% of theoverall length of the permeable shell 40 for some embodiments. Such aconfiguration may allow for the distal end 34 to flex downward towardthe proximal end 32 when the device 10 meets resistance at the distalend 34 and thus may provide longitudinal conformance. The filaments 14may be shaped in some embodiments such that there are no portions thatare without curvature over a distance of more than about 2 mm. Thus, forsome embodiments, each filament 14 may have a substantially continuouscurvature. This substantially continuous curvature may provide smoothdeployment and may reduce the risk of vessel perforation. For someembodiments, one of the ends 32 or 34 may be retracted or everted to agreater extent than the other so as to be more longitudinally or axiallyconformal than the other end.

The first radius 88 and second radius 90 of the permeable shell 40 maybe between about 0.12 mm to about 3 mm for some embodiments. For someembodiments, the distance between the proximal end 32 and distal end 34may be more than about 60% of the overall length of the expandedpermeable shell 40. Thus, the largest longitudinal distance between theinner surfaces may be about 60% to about 90% of the longitudinal lengthof the outer surfaces or the overall length of device 10. A gap betweenthe hubs 66 and 68 at the proximal end 32 and distal end 34 may allowfor the distal hub 66 to flex downward toward the proximal hub 68 whenthe device 10 meets resistance at the distal end and thus provideslongitudinal conformance. The filaments 14 may be shaped such that thereare no portions that are without curvature over a distance of more thanabout 2 mm. Thus, for some embodiments, each filament 14 may have asubstantially continuous curvature. This substantially continuouscurvature may provide smooth deployment and may reduce the risk ofvessel perforation. The distal end 34 may be retracted or everted to agreater extent than the proximal end 32 such that the distal end portionof the permeable shell 40 may be more radially conformal than theproximal end portion. Conformability of a distal end portion may providebetter device conformance to irregular shaped aneurysms or othervascular defects. A convex surface of the device may flex inward forminga concave surface to conform to curvature of a vascular site.

FIG. 10 shows an enlarged view of the filaments 14 disposed within aproximal hub 68 of the device 10 with the filaments 14 of two differentsizes constrained and tightly packed by an outer ring of the proximalhub 68. The tether member 72 may optionally be disposed within a middleportion of the filaments 14 or within the cavity 70 of the proximal hub68 proximal of the proximal ends 60 of the filaments 14 as shown in FIG.6. The distal end of the tether 72 may be secured with a knot 92 formedin the distal end thereof which is mechanically captured in the cavity70 of the proximal hub 68 formed by a proximal shoulder portion 94 ofthe proximal hub 68. The knotted distal end 92 of the tether 72 may alsobe secured by bonding or potting of the distal end of the tether 72within the cavity 70 and optionally amongst the proximal ends 60 of thefilaments 14 with mechanical compression, adhesive bonding, welding,soldering, brazing or the like. The tether embodiment 72 shown in FIG. 6has a knotted distal end 92 potted in the cavity of the proximal hub 68with an adhesive. Such a tether 72 may be a dissolvable, severable orreleasable tether that may be part of a delivery apparatus 110 used todeploy the device 10 as shown in FIG. 11 and FIGS. 23-26. FIG. 10 alsoshows the large filaments 48 and small filaments 50 disposed within andconstrained by the proximal hub 68 which may be configured to secure thelarge and small filaments 48 and 50 in place relative to each otherwithin the outer ring of the proximal hub 68.

FIGS. 7 and 8 illustrate some configuration embodiments of braidedfilaments 14 of a permeable shell 40 of the device 10 for treatment of apatient's vasculature. The braid structure in each embodiment is shownwith a circular shape 100 disposed within a pore 64 of a woven orbraided structure with the circular shape 100 making contact with eachadjacent filament segment. The pore opening size may be determined atleast in part by the size of the filament elements 14 of the braid, theangle overlapping filaments make relative to each other and the picksper inch of the braid structure. For some embodiments, the cells oropenings 64 may have an elongated substantially diamond shape as shownin FIG. 7, and the pores or openings 64 of the permeable shell 40 mayhave a substantially more square shape toward a middle portion 30 of thedevice 10, as shown in FIG. 8. The diamond shaped pores or openings 64may have a length substantially greater than the width particularly nearthe hubs 66 and 68. In some embodiments, the ratio of diamond shapedpore or opening length to width may exceed a ratio of 3 to 1 for somecells. The diamond-shaped openings 64 may have lengths greater than thewidth thus having an aspect ratio, defined as Length/Width of greaterthan 1. The openings 64 near the hubs 66 and 68 may have substantiallylarger aspect ratios than those farther from the hubs as shown in FIG.7. The aspect ratio of openings 64 adjacent the hubs may be greater thanabout 4 to 1. The aspect ratio of openings 64 near the largest diametermay be between about 0.75 to 1 and about 2 to 1 for some embodiments.For some embodiments, the aspect ratio of the openings 64 in thepermeable shell 40 may be about 0.5 to 1 to about 2 to 1.

The pore size defined by the largest circular shapes 100 that may bedisposed within openings 64 of the braided structure of the permeableshell 40 without displacing or distorting the filaments 14 surroundingthe opening 64 may range in size from about 0.005 inches to about 0.01inches, more specifically, about 0.006 inches to about 0.009 inches,even more specifically, about 0.007 inches to about 0.008 inches forsome embodiments. In addition, at least some of the openings 64 formedbetween adjacent filaments 14 of the permeable shell 40 of the device 10may be configured to allow blood flow through the openings 64 only at avelocity below a thrombotic threshold velocity. For some embodiments,the largest openings 64 in the permeable shell structure 40 may beconfigured to allow blood flow through the openings 64 only at avelocity below a thrombotic threshold velocity. As discussed above, thepore size may be less than about 0.016 inches, more specifically, lessthan about 0.012 inches for some embodiments. For some embodiments, theopenings 64 formed between adjacent filaments 14 may be about 0.005inches to about 0.04 inches.

Referring to FIGS. 12-15, a delivery apparatus embodiment 110 of thedelivery system 112 of FIG. 11 is shown in more detail. The apparatus110 includes an elongate core wire 114 that extends from a proximal end116 of the apparatus 110 to a distal section 118 of the apparatus 110 asshown in FIG. 12. The core wire 114 is configured to provide sufficientcolumn strength to push a constrained device 10 for treatment of apatient's vasculature through an inner lumen 120 of the microcatheter 61of the delivery system 112 as shown in FIG. 11. The core wire 114 alsohas sufficient tensile strength to withdraw or proximally retract thedevice 10 from a position outside the microcatheter 61 and axiallywithin the inner lumen 120 of the microcatheter 61. The tether 72 thatextends proximally from the proximal hub 68 is secured to the distal endof the core wire 114 with a length of shrinkable tubing 122 that isdisposed over a portion of the tether 72 and a distal section of thecore wire 114 and shrunk over both as shown in FIG. 13, although anyother suitable means of securement may be used.

A heater coil 124 electrically coupled to a first conductor 126 and asecond conductor 128 is disposed over a distal most portion of thetether 72. The heater coil 124 may also be covered with a length ofpolymer tubing 130 disposed over the heater coil 124 distal of the heatshrink tubing 122 that serves to act as a heat shield and minimizes theleakage of heat from the heater coil 124 into the environment, such asthe patient's blood stream, around the delivery apparatus 110. Once theheat shrink tubing 122 and insulating polymer tubing 130 have beensecured to the distal section 118 of the apparatus 110, the proximalportion of the tether 72 disposed proximal of the heat shrink tubing 122may be trimmed as shown in FIG. 13. An over coil 132 that extends from adistal end 134 of the delivery apparatus 110 to a proximal section 136of the apparatus 110 may then be disposed over the heater coil 124, corewire 114, tether 72, first conductor 126 and second conductor 128 tohold these elements together, produce a low friction outer surface andmaintain a desired flexibility of the delivery apparatus 110. Theproximal section 136 of the apparatus 110 includes the proximal terminusof the over coil 132 which is disposed distal of a first contact 138 andsecond contact 140 which are circumferentially disposed about theproximal section 136 of the core wire 114, insulated therefrom, andelectrically coupled to the first conductor 126 and second conductor128, respectively as shown in FIG. 15.

The heater coil 124 may be configured to receive electric currentsupplied through the first conductor 126 and second conductor 128 froman electrical energy source 142 coupled to the first contact 138 andsecond contact 140 at the proximal section 136 of the apparatus 110. Theelectrical current passed through the heater coil 124 heats the heatercoil to a temperature above the melting point of the tether material 72so as to melt the tether 72 and sever it upon deployment of the device10.

Embodiments of the delivery apparatus 110 may generally have a lengthgreater than the overall length of a microcatheter 61 to be used for thedelivery system 112. This relationship allows the delivery apparatus 110to extend, along with the device 10 secured to the distal end thereof,from the distal port of the inner lumen 120 of the microcatheter 61while having sufficient length extending from a proximal end 150 of themicrocatheter 61, shown in FIG. 17 discussed below, to enablemanipulation thereof by a physician. For some embodiments, the length ofthe delivery apparatus 110 may be about 170 cm to about 200 cm. The corewire 114 may be made from any suitable high strength material such asstainless steel, NiTi alloy, or the like. Embodiments of the core wire114 may have an outer diameter or transverse dimension of about 0.010inch to about 0.015 inch. The over coil 132 may have an outer diameteror transverse dimension of about 0.018 inch to about 0.03 inch. Althoughthe apparatus embodiment 110 shown in FIGS. 12-15 is activated byelectrical energy passed through a conductor pair, a similarconfiguration that utilizes light energy passed through a fiber optic orany other suitable arrangement could be used to remotely heat a distalheating member or element such as the heater coil 124 to sever thedistal portion of the tether 72. In addition, other delivery apparatusembodiments are discussed and incorporated herein that may also be usedfor any of the device embodiments 10 for treatment of a patient'svasculature discussed herein.

Other delivery and positioning system embodiments may provide for theability to rotate a device for treatment of a patient's vasculaturein-vivo without translating torque along the entire length of thedelivery apparatus. Some embodiments for delivery and positioning ofdevices 10 are described in co-owned International PCT PatentApplication No. PCT/US2008/065694 incorporated above. The delivery andpositioning apparatus may include a distal rotating member that allowsrotational positioning of the device. The delivery and positioningapparatus may include a distal rotating member which rotates an implantin-vivo without the transmission of torque along the entire length ofthe apparatus. Optionally, delivery system may also rotate the implantwithout the transmission of torque in the intermediate portion betweenthe proximal end and the distal rotatable end. The delivery andpositioning apparatus may be releasably secured to any suitable portionof the device for treatment of a patient's vasculature.

Device embodiments discussed herein may be releasable from any suitableflexible, elongate delivery apparatus or actuator such as a guidewire orguidewire-like structure. The release of device embodiments from such adelivery apparatus may be activated by a thermal mechanism, as discussedabove, electrolytic mechanism, hydraulic mechanism, shape memorymaterial mechanism, or any other mechanism known in the art ofendovascular implant deployment.

Embodiments for deployment and release of therapeutic devices, such asdeployment of embolic devices or stents within the vasculature of apatient, may include connecting such a device via a releasableconnection to a distal portion of a pusher or other delivery apparatusmember. The therapeutic device 10 may be detachably mounted to thedistal portion of the apparatus by a filamentary tether 72, string,thread, wire, suture, fiber, or the like, which may be referred to aboveas the tether. The tether 72 may be in the form of a monofilament, rod,ribbon, hollow tube, or the like. Some embodiments of the tether mayhave a diameter or maximum thickness of between about 0.05 mm and 0.2mm. The tether 72 may be configured to be able to withstand a maximumtensile load of between about 0.5 kg and 5 kg. For some embodiments, dueto the mass of the device 10 being deployed which may be substantiallygreater than some embolic devices, some known detachment devices maylack sufficient tensile strength to be used for some embodimentsdiscussed herein. As such, it may be desirable to use small very highstrength fibers for some tether embodiments having a “load at break”greater than about 15 Newtons. For some embodiments, a tether made froma material known as Dyneema Purity available from Royal DSM, Heerlen,Netherlands may be used.

The tether 72 may be severed by the input of energy such as electriccurrent to a heating element causing release of the therapeutic device.For some embodiments, the heating element may be a coil of wire withhigh electrical resistivity such as a platinum-tungsten alloy. Thetether member may pass through or be positioned adjacent the heaterelement. The heater may be contained substantially within the distalportion of the delivery apparatus to provide thermal insulation toreduce the potential for thermal damage to the surrounding tissuesduring detachment. In another embodiment, current may pass through thetether which also acts as a heating element.

Many materials may be used to make tether embodiments 72 includingpolymers, metals and composites thereof. One class of materials that maybe useful for tethers includes polymers such as polyolefin, polyolefinelastomer such as polyethylene, polyester (PET), polyamide (Nylon),polyurethane, polypropylene, block copolymer such as PEBAX or Hytrel,and ethylene vinyl alcohol (EVA); or rubbery materials such as silicone,latex, and Kraton. In some cases, the polymer may also be cross-linkedwith radiation to manipulate its tensile strength and melt temperature.Another class of materials that may be used for tether embodiment mayinclude metals such as nickel titanium alloy (Nitinol), gold, platinum,tantalum and steel. Other materials that may be useful for tetherconstruction includes wholly aromatic polyester polymers which areliquid crystal polymers (LCP) that may provide high performanceproperties and are highly inert. A commercially available LCP polymer isVectran, which is produced by Kuraray Co. (Tokyo, Japan). The selectionof the material may depend on the melting or softening temperature, thepower used for detachment, and the body treatment site. The tether maybe joined to the implant and/or the pusher by crimping, welding, knottying, soldering, adhesive bonding, or other means known in the art.

It should be noted also that many variations of filament and proximalhub construction such as is detailed above with regard to FIG. 10 may beused for useful embodiments of a device for treatment of a patient'svasculature 10. FIG. 16 shows an enlarged view in transverse crosssection of a proximal hub configuration. For the embodiment shown, thefilaments 14 are disposed within a proximal hub 68 or end portion of thedevice 10 with the filaments 14 constrained and tightly packed by anouter ring of the proximal hub 68. A tether member 72 may be disposedwithin a middle portion of the filaments 14 or within a cavity of theproximal hub 68 proximal of the proximal ends 60 of the filaments 14.Such a tether 72 may be a dissolvable, severable or releasable tetherthat may be part of a release apparatus as discussed above used todeploy the device.

FIG. 16 illustrates in transverse cross section an embodiment of aproximal hub 68 showing the configuration of filaments which may betightly packed and radially constrained by an inside surface of theproximal hub 68. In some embodiments, the braided or woven structure ofthe permeable shell 40 formed from such filaments 14 may be constructedusing a large number of small filaments. The number of filaments 14 maybe greater than 125 and may also be between about 80 filaments and about180 filaments. As discussed above, the total number of filaments 14 forsome embodiments may be about 70 filaments to about 300 filaments, morespecifically, about 100 filaments to about 200 filaments. In someembodiments, the braided structure of the permeable shell 40 may beconstructed with two or more sizes of filaments 14. For example, thestructure may have several larger filaments that provide structuralsupport and several smaller filaments that provide the desired pore sizeand density and thus flow resistance to achieve a thrombotic thresholdvelocity in some cases. For some embodiments, small filaments 50 of thepermeable shell 40 may have a transverse dimension or diameter of about0.0006 inches to about 0.002 inches for some embodiments and about0.0004 inches to about 0.001 inches in other embodiments. The largefilaments 48 may have a transverse dimension or diameter of about 0.0015inches to about 0.004 inches in some embodiments and about 0.001 inchesto about 0.004 inches in other embodiments. The filaments 14 may bebraided in a plain weave that is one under, one over structure (shown inFIGS. 7 and 8) or a supplementary weave; more than one warp interlacewith one or more than one weft. The pick count may be varied betweenabout 25 and 200 picks per inch (PPI).

For some embodiments, the permeable shell 40 or portions thereof may beporous and may be highly permeable to liquids. In contrast to mostvascular prosthesis fabrics or grafts which typically have a waterpermeability below 2,000 ml/min/cm² when measured at a pressure of 120mmHg, the permeable shell 40 of some embodiments discussed herein mayhave a water permeability greater than about 2,000 mI/min/cm², in somecases greater than about 2,500 ml/min/cm². For some embodiments, waterpermeability of the permeable shell 40 or portions thereof may bebetween about 2,000 and 10,000 ml/min/cm², more specifically, about2,000 ml/min/cm² to about 15,000 mI/min/cm², when measured at a pressureof 120 mmHg.

Device embodiments and components thereof may include metals, polymers,biologic materials and composites thereof. Suitable metals includezirconium-based alloys, cobalt-chrome alloys, nickel-titanium alloys,platinum, tantalum, stainless steel, titanium, gold, and tungsten.Potentially suitable polymers include but are not limited to acrylics,silk, silicones, polyvinyl alcohol, polypropylene, polyvinyl alcohol,polyesters (e.g. polyethylene terephthalate or PET), PolyEtherEtherKetone (PEEK), polytetrafluoroethylene (PTFE), polycarbonate urethane(PCU) and polyurethane (PU). Device embodiments may include a materialthat degrades or is absorbed or eroded by the body. A bioresorbable(e.g., breaks down and is absorbed by a cell, tissue, or other mechanismwithin the body) or bioabsorbable (similar to bioresorbable) materialmay be used. Alternatively, a bioerodable (e.g., erodes or degrades overtime by contact with surrounding tissue fluids, through cellularactivity or other physiological degradation mechanisms), biodegradable(e.g., degrades over time by enzymatic or hydrolytic action, or othermechanism in the body), or dissolvable material may be employed. Each ofthese terms is interpreted to be interchangeable. bioabsorbable polymer.Potentially suitable bioabsorbable materials include polylactic acid(PLA), poly(alpha-hydroxy acid) such as poly-L-lactide (PLLA),poly-D-lactide (PDLA), polyglycolide (PGA), polydioxanone,polycaprolactone, polygluconate, polylactic acid-polyethylene oxidecopolymers, modified cellulose, collagen, poly(hydroxybutyrate),polyanhydride, polyphosphoester, poly(amino acids), or related copolymermaterials. An absorbable composite fiber may be made by combining areinforcement fiber made from a copolymer of about 18% glycolic acid andabout 82% lactic acid with a matrix material consisting of a blend ofthe above copolymer with about 20% polycaprolactone (PCL).

In any of the suitable device embodiments 10 discussed herein, thepermeable shell structure 40 may include one or more fixation elementsor surfaces to facilitate fixation of the device within a blood vesselor other vascular site. The fixation elements may comprise hooks, barbs,protrusions, pores, microfeatures, texturing, bioadhesives orcombinations thereof. Embodiments of the support structure may befabricated from a tube of metal where portions are removed. The removalof material may be done by laser, electrical discharge machining (EDM),photochemical etching and traditional machining techniques. In any ofthe described embodiments, the support structure may be constructed witha plurality of wires, cut or etched from a sheet of a material, cut oretched from a tube or a combination thereof as in the art of vascularstent fabrication.

Permeable shell embodiments 40 may be formed at least in part of wire,ribbon, or other filamentary elements 14. These filamentary elements 14may have circular, elliptical, ovoid, square, rectangular, or triangularcross-sections. Permeable shell embodiments 40 may also be formed usingconventional machining, laser cutting, electrical discharge machining(EDM) or photochemical machining (PCM). If made of a metal, it may beformed from either metallic tubes or sheet material.

Device embodiments 10 discussed herein may be delivered and deployedfrom a delivery and positioning system 112 that includes a microcatheter61, such as the type of microcatheter 61 that is known in the art ofneurovascular navigation and therapy. Device embodiments for treatmentof a patient's vasculature 10 may be elastically collapsed andrestrained by a tube or other radial restraint, such as an inner lumen120 of a microcatheter 61, for delivery and deployment. Themicrocatheter 61 may generally be inserted through a small incision 152accessing a peripheral blood vessel such as the femoral artery orbrachial artery. The microcatheter 61 may be delivered or otherwisenavigated to a desired treatment site 154 from a position outside thepatient's body 156 over a guidewire 159 under fluoroscopy or by othersuitable guiding methods. The guidewire 159 may be removed during such aprocedure to allow insertion of the device 10 secured to a deliveryapparatus 110 of the delivery system 112 through the inner lumen 120 ofa microcatheter 61 in some cases. FIG. 17 illustrates a schematic viewof a patient 158 undergoing treatment of a vascular defect 160 as shownin FIG. 18. An access sheath 162 is shown disposed within either aradial artery 164 or femoral artery 166 of the patient 158 with adelivery system 112 that includes a microcatheter 61 and deliveryapparatus 110 disposed within the access sheath 162. The delivery system112 is shown extending distally into the vasculature of the patient'sbrain adjacent a vascular defect 160 in the patient's brain.

Access to a variety of blood vessels of a patient may be established,including arteries such as the femoral artery 166, radial artery 164,and the like in order to achieve percutaneous access to a vasculardefect 160. In general, the patient 158 may be prepared for surgery andthe access artery is exposed via a small surgical incision 152 andaccess to the lumen is gained using the Seldinger technique where anintroducing needle is used to place a wire over which a dilator orseries of dilators dilates a vessel allowing an introducer sheath 162 tobe inserted into the vessel. This would allow the device to be usedpercutaneously. With an introducer sheath 162 in place, a guidingcatheter 168 is then used to provide a safe passageway from the entrysite to a region near the target site 154 to be treated. For example, intreating a site in the human brain, a guiding catheter 168 would bechosen which would extend from the entry site 152 at the femoral arteryup through the large arteries extending around the heart through theaortic arch, and downstream through one of the arteries extending fromthe upper side of the aorta such as the carotid artery 170. Typically, aguidewire 159 and neurovascular microcatheter 61 are then placed throughthe guiding catheter 168 and advanced through the patient's vasculature,until a distal end 151 of the microcatheter 61 is disposed adjacent orwithin the target vascular defect 160, such as an aneurysm. Exemplaryguidewires 159 for neurovascular use include the Synchro2® made byBoston Scientific and the Glidewire Gold Neuro® made by MicroVentionTerumo. Typical guidewire sizes may include 0.014 inches and 0.018inches. Once the distal end 151 of the catheter 61 is positioned at thesite, often by locating its distal end through the use of radiopaquemarker material and fluoroscopy, the catheter is cleared. For example,if a guidewire 159 has been used to position the microcatheter 61, it iswithdrawn from the catheter 61 and then the implant delivery apparatus110 is advanced through the microcatheter 61.

Delivery and deployment of device embodiments 10 discussed herein may becarried out by first compressing the device 10 to a radially constrainedand longitudinally flexible state as shown in FIG. 11. The device 10 maythen be delivered to a desired treatment site 154 while disposed withinthe microcatheter 61, and then ejected or otherwise deployed from adistal end 151 of the microcatheter 61. In other method embodiments, themicrocatheter 61 may first be navigated to a desired treatment site 154over a guidewire 159 or by other suitable navigation techniques. Thedistal end of the microcatheter 61 may be positioned such that a distalport of the microcatheter 61 is directed towards or disposed within avascular defect 160 to be treated and the guidewire 159 withdrawn. Thedevice 10 secured to a suitable delivery apparatus 110 may then beradially constrained, inserted into a proximal portion of the innerlumen 120 of the microcatheter 61 and distally advanced to the vasculardefect 160 through the inner lumen 120.

Once disposed within the vascular defect 160, the device 10 may thenallowed to assume an expanded relaxed or partially relaxed state withthe permeable shell 40 of the device spanning or partially spanning aportion of the vascular defect 160 or the entire vascular defect 160.The device 10 may also be activated by the application of an energysource to assume an expanded deployed configuration once ejected fromthe distal section of the microcatheter 61 for some embodiments. Oncethe device 10 is deployed at a desired treatment site 154, themicrocatheter 61 may then be withdrawn.

Some embodiments of devices for the treatment of a patient's vasculature10 discussed herein may be directed to the treatment of specific typesof defects of a patient's vasculature. For example, referring to FIG.18, an aneurysm 160 commonly referred to as a terminal aneurysm is shownin section. Terminal aneurysms occur typically at bifurcations in apatient's vasculature where blood flow, indicated by the arrows 172,from a supply vessel splits into two or more branch vessels directedaway from each other. The main flow of blood from the supply vessel 174,such as a basilar artery, sometimes impinges on the vessel where thevessel diverges and where the aneurysm sack forms. Terminal aneurysmsmay have a well defined neck structure where the profile of the aneurysm160 narrows adjacent the nominal vessel profile, but other terminalaneurysm embodiments may have a less defined neck structure or no neckstructure. FIG. 19 illustrates a typical berry type aneurysm 160 insection where a portion of a wall of a nominal vessel section weakensand expands into a sack like structure ballooning away from the nominalvessel surface and profile. Some berry type aneurysms may have a welldefined neck structure as shown in FIG. 19, but others may have a lessdefined neck structure or none at all. FIG. 19 also shows some optionalprocedures wherein a stent 173 or other type of support has beendeployed in the parent vessel 174 adjacent the aneurysm. Also, shown isembolic material 176 being deposited into the aneurysm 160 through amicrocatheter 61. Either or both of the stent 173 and embolic material176 may be so deployed either before or after the deployment of a devicefor treatment of a patient's vasculature 10.

Prior to delivery and deployment of a device for treatment of apatient's vasculature 10, it may be desirable for the treating physicianto choose an appropriately sized device 10 to optimize the treatmentresults. Some embodiments of treatment may include estimating a volumeof a vascular site or defect 160 to be treated and selecting a device 10with a volume that is substantially the same volume or slightlyover-sized relative to the volume of the vascular site or defect 160.The volume of the vascular defect 160 to be occluded may be determinedusing three-dimensional angiography or other similar imaging techniquesalong with software which calculates the volume of a selected region.The amount of over-sizing may be between about 2% and 15% of themeasured volume. In some embodiments, such as a very irregular shapedaneurysm, it may be desirable to under-size the volume of the device 10.Small lobes or “daughter aneurysms” may be excluded from the volume,defining a truncated volume which may be only partially filled by thedevice without affecting the outcome. A device 10 deployed within suchan irregularly shaped aneurysm 160 is shown in FIG. 28 discussed below.Such a method embodiment may also include implanting or deploying thedevice 10 so that the vascular defect 160 is substantially filledvolumetrically by a combination of device and blood contained therein.The device 10 may be configured to be sufficiently conformal to adapt toirregular shaped vascular defects 160 so that at least about 75%, insome cases about 80%, of the vascular defect volume is occluded by acombination of device 10 and blood contained therein.

In particular, for some treatment embodiments, it may be desirable tochoose a device 10 that is properly oversized in a transverse dimensionso as to achieve a desired conformance, radial force and fit afterdeployment of the device 10. FIGS. 20-22 illustrate a schematicrepresentation of how a device 10 may be chosen for a proper fit afterdeployment that is initially oversized in a transverse dimension by atleast about 10% of the largest transverse dimension of the vasculardefect 160 and sometimes up to about 100% of the largest transversedimension. For some embodiments, the device 10 may be oversized a smallamount (e.g. less than about 1.5 mm) in relation to measured dimensionsfor the width, height or neck diameter of the vascular defect 160.

In FIG. 20, a vascular defect 160 in the form of a cerebral aneurysm isshown with horizontal arrows 180 and vertical arrows 182 indicating theapproximate largest interior dimensions of the defect 160. Arrow 180extending horizontally indicates the largest transverse dimension of thedefect 160. In FIG. 21, a dashed outline 184 of a device for treatmentof the vascular defect 10 is shown superimposed over the vascular defect160 of FIG. 20 illustrating how a device 10 that has been chosen to beapproximately 20% oversized in a transverse dimension would look in itsunconstrained, relaxed state. FIG. 22 illustrates how the device 10which is indicated by the dashed line 184 of FIG. 21 might conform tothe interior surface of the vascular defect 160 after deployment wherebythe nominal transverse dimension of the device 10 in a relaxedunconstrained state has now been slightly constrained by the inwardradial force 185 exerted by the vascular defect 160 on the device 10. Inresponse, as the filaments 14 of the device 10 and thus the permeableshell 40 made therefrom have a constant length, the device 10 hasassumed a slightly elongated shape in the axial or longitudinal axis ofthe device 10 so as to elongate and better fill the interior volume ofthe defect 160 as indicated by the downward arrow 186 in FIG. 22.

Once a properly sized device 10 has been selected, the delivery anddeployment process may then proceed. It should also be noted also thatthe properties of the device embodiments 10 and delivery systemembodiments 112 discussed herein generally allow for retraction of adevice 10 after initial deployment into a defect 160, but beforedetachment of the device 10. Therefore, it may also be possible anddesirable to withdraw or retrieve an initially deployed device 10 afterthe fit within the defect 160 has been evaluated in favor of adifferently sized device 10. An example of a terminal aneurysm 160 isshown in FIG. 23 in section. The tip 151 of a catheter, such as amicrocatheter 61 may be advanced into or adjacent the vascular site ordefect 160 (e.g. aneurysm) as shown in FIG. 24. For some embodiments, anembolic coil or other vaso-occlusive device or material 176 (as shownfor example in FIG. 19) may optionally be placed within the aneurysm 160to provide a framework for receiving the device 10. In addition, a stent173 may be placed within a parent vessel 174 of some aneurysmssubstantially crossing the aneurysm neck prior to or during delivery ofdevices for treatment of a patient's vasculature discussed herein (alsoas shown for example in FIG. 19). An example of a suitable microcatheter61 having an inner lumen diameter of about 0.020 inches to about 0.022inches is the Rapid Transit® manufactured by Cordis Corporation.Examples of some suitable microcatheters 61 may include microcathetershaving an inner lumen diameter of about 0.026 inch to about 0.028 inch,such as the Rebar® by Ev3 Company, the Renegade Hi-Flow® by BostonScientific Corporation, and the Mass Transit® by Cordis Corporation.Suitable microcatheters having an inner lumen diameter of about 0.031inch to about 0.033 inch may include the Marksmen® by Chestnut MedicalTechnologies, Inc. and the Vasco 28® by Bait Extrusion. A suitablemicrocatheter 61 having an inner lumen diameter of about 0.039 inch toabout 0.041 inch includes the Vasco 35 by Bait Extrusion. Thesemicrocatheters 61 are listed as exemplary embodiments only, othersuitable microcatheters may also be used with any of the embodimentsdiscussed herein.

Detachment of the device 10 from the delivery apparatus 110 may becontrolled by a control switch 188 disposed at a proximal end of thedelivery system 112, which may also be coupled to an energy source 142,which severs the tether 72 that secures the proximal hub 68 of thedevice 10 to the delivery apparatus 110. While disposed within themicrocatheter 61 or other suitable delivery system 112, as shown in FIG.11, the filaments 14 of the permeable shell 40 may take on an elongated,non-everted configuration substantially parallel to each other and alongitudinal axis of the catheter 61. Once the device 10 is pushed outof the distal port of the microcatheter 61, or the radial constraint isotherwise removed, the distal ends 62 of the filaments 14 may thenaxially contract towards each other so as to assume the globular evertedconfiguration within the vascular defect 160 as shown in FIG. 25.

The device 10 may be inserted through the microcatheter 61 such that thecatheter lumen 120 restrains radial expansion of the device 10 duringdelivery. Once the distal tip or deployment port of the delivery system112 is positioned in a desirable location adjacent or within a vasculardefect 160, the device 10 may be deployed out the distal end of thecatheter 61 thus allowing the device to begin to radially expand asshown in FIG. 25. As the device 10 emerges from the distal end of thedelivery system 112, the device 10 expands to an expanded state withinthe vascular defect 160, but may be at least partially constrained by aninterior surface of the vascular defect 160.

Upon full deployment, radial expansion of the device 10 may serve tosecure the device 10 within the vascular defect 160 and also deploy thepermeable shell 40 across at least a portion of an opening 190 (e.g.aneurysm neck) so as to at least partially isolate the vascular defect160 from flow, pressure or both of the patient's vasculature adjacentthe vascular defect 160 as shown in FIG. 26. The conformability of thedevice 10, particularly in the neck region 190 may provide for improvedsealing. For some embodiments, once deployed, the permeable shell 40 maysubstantially slow flow of fluids and impede flow into the vascular siteand thus reduce pressure within the vascular defect 160. For someembodiments, the device 10 may be implanted substantially within thevascular defect 160, however, in some embodiments, a portion of thedevice 10 may extend into the defect opening or neck 190 or into branchvessels.

One exemplary case study that has been conducted includes a procedureperformed on a female canine where an aneurysm was surgically created inthe subject canine. The target aneurysm prior to treatment had a maximumtransverse dimension of about 8 mm, a length of about 10 mm and a neckmeasurement of about 5.6 mm. The device 10 deployed included a permeableshell 40 formed of 144 resilient filaments having a transverse diameterof about 0.0015 inches braided into a globular structure having atransverse dimension of about 10 mm and a longitudinal length of about 7mm in a relaxed expanded state. The maximum size 100 of the pores 64 ofthe expanded deployed permeable shell 40 was about 0.013 inches. Thedevice was delivered to the target aneurysm using a 5 Fr. Guider SoftipXF guide catheter made by Boston Scientific. The maximum size 100 of thepores 64 of the portion of the expanded deployed permeable shell 40 thatspanned the neck of the aneurysm again was about 0.013 inches. Fiveminutes after detachment from the delivery system, the device 10 hadproduced acute occlusion of the aneurysm.

Another exemplary case study conducted involved treatment of asurgically created aneurysm in a New Zealand White Rabbit. The targetaneurysm prior to treatment had a maximum transverse dimension of about3.6 mm, length of about 5.8 mm and a neck measurement of about 3.4 mm.The device 10 deployed included a permeable shell formed of 144resilient filaments having a transverse diameter of about 0.001 inchesbraided into a globular structure having a transverse dimension of about4 mm and a length of about 5 mm in a relaxed expanded state. The poresize 100 of the portion of the braided mesh of the expanded deployedpermeable shell 40 that was configured to span the neck of the vasculardefect was about 0.005 inches. The device was delivered to thesurgically created aneurysm with a 5 Fr. Envoy STR guide cathetermanufactured by Cordis Neurovascular. A Renegade Hi-Flo microcathetermanufactured by Boston Scientific having an inner lumen diameter ofabout 0.027 inches was then inserted through the guide catheter andserved as a conduit for delivery of the device 10 secured to a distalend of a delivery apparatus. Once the device 10 was deployed within thevascular defect 160, the vascular defect 160 achieved at least partialocclusion at 5 minutes from implantation. However, due to thesensitivity of the subject animal to angiographic injection andmeasurement, no further data was taken during the procedure. Completeocclusion was observed for the device when examined at 3 weeks from theprocedure.

For some embodiments, as discussed above, the device 10 may bemanipulated by the user to position the device 10 within the vascularsite or defect 160 during or after deployment but prior to detachment.For some embodiments, the device 10 may be rotated in order to achieve adesired position of the device 10 and, more specifically, a desiredposition of the permeable shell 40, prior to or during deployment of thedevice 10. For some embodiments, the device 10 may be rotated about alongitudinal axis of the delivery system 112 with or without thetransmission or manifestation of torque being exhibited along a middleportion of a delivery catheter being used for the delivery. It may bedesirable in some circumstances to determine whether acute occlusion ofthe vascular defect 160 has occurred prior to detachment of the device10 from the delivery apparatus 110 of the delivery system 112. Thesedelivery and deployment methods may be used for deployment within berryaneurysms, terminal aneurysms, or any other suitable vascular defectembodiments 160. Some method embodiments include deploying the device 10at a confluence of three vessels of the patient's vasculature that forma bifurcation such that the permeable shell 40 of the device 10substantially covers the neck of a terminal aneurysm. Once the physicianis satisfied with the deployment, size and position of the device 10,the device 10 may then be detached by actuation of the control switch188 by the methods described above and shown in FIG. 26. Thereafter, thedevice 10 is in an implanted state within the vascular defect 160 toeffect treatment thereof.

FIG. 27 illustrates another configuration of a deployed and implanteddevice in a patient's vascular defect 160. While the implantationconfiguration shown in FIG. 26 indicates a configuration whereby thelongitudinal axis 46 of the device 10 is substantially aligned with alongitudinal axis of the defect 160, other suitable and clinicallyeffective implantation embodiments may be used. For example, FIG. 27shows an implantation embodiment whereby the longitudinal axis 46 of theimplanted device 10 is canted at an angle of about 10 degrees to about90 degrees relative to a longitudinal axis of the target vascular defect160. Such an alternative implantation configuration may also be usefulin achieving a desired clinical outcome with acute occlusion of thevascular defect 160 in some cases and restoration of normal blood flowadjacent the treated vascular defect. FIG. 28 illustrates a device 10implanted in an irregularly shaped vascular defect 160. The aneurysm 160shown has at least two distinct lobes 192 extending from the mainaneurysm cavity. The two lobes 192 shown are unfilled by the deployedvascular device 10, yet the lobes 192 are still isolated from the parentvessel of the patient's body due to the occlusion of the aneurysm neckportion 190.

Markers, such as radiopaque markers, on the device 10 or delivery system112 may be used in conjunction with external imaging equipment (e.g.,x-ray) to facilitate positioning of the device or delivery system duringdeployment. Once the device is properly positioned, the device 10 may bedetached by the user. For some embodiments, the detachment of the device10 from the delivery apparatus 110 of the delivery system 112 may beaffected by the delivery of energy (e.g. heat, radiofrequency,ultrasound, vibrational, or laser) to a junction or release mechanismbetween the device 10 and the delivery apparatus 110. Once the device 10has been detached, the delivery system 112 may be withdrawn from thepatient's vasculature or patient's body 158. For some embodiments, astent 173 may be place within the parent vessel substantially crossingthe aneurysm neck 190 after delivery of the device 10 as shown in FIG.19 for illustration.

For some embodiments, a biologically active agent or a passivetherapeutic agent may be released from a responsive material componentof the device 10. The agent release may be affected by one or more ofthe body's environmental parameters or energy may be delivered (from aninternal or external source) to the device 10. Hemostasis may occurwithin the vascular defect 160 as a result of the isolation of thevascular defect 160, ultimately leading to clotting and substantialocclusion of the vascular defect 160 by a combination of thromboticmaterial and the device 10. For some embodiments, thrombosis within thevascular defect 160 may be facilitated by agents released from thedevice 10 and/or drugs or other therapeutic agents delivered to thepatient.

For some embodiments, once the device 10 has been deployed, theattachment of platelets to the permeable shell 40 may be inhibited andthe formation of clot within an interior space of the vascular defect160, device, or both promoted or otherwise facilitated with a suitablechoice of thrombogenic coatings, anti-thrombogenic coatings or any othersuitable coatings (not shown) which may be disposed on any portion ofthe device 10 for some embodiments, including an outer surface of thefilaments 14 or the hubs 66 and 68. Such a coating or coatings may beapplied to any suitable portion of the permeable shell 40. Energy formsmay also be applied through the delivery apparatus 110 and/or a separatecatheter to facilitate fixation and/or healing of the device 10 adjacentthe vascular defect 160 for some embodiments. One or more embolicdevices or embolic material 176 may also optionally be delivered intothe vascular defect 160 adjacent permeable shell portion that spans theneck or opening 190 of the vascular defect 160 after the device 10 hasbeen deployed. For some embodiments, a stent or stent-like supportdevice 173 may be implanted or deployed in a parent vessel adjacent thedefect 160 such that it spans across the vascular defect 160 prior to orafter deployment of the vascular defect treatment device 10.

In any of the above embodiments, the device 10 may have sufficientradial compliance so as to be readily retrievable or retractable into atypical microcatheter 61. The proximal portion of the device 10, or thedevice as a whole for some embodiments, may be engineered or modified bythe use of reduced diameter filaments, tapered filaments, or filamentsoriented for radial flexure so that the device 10 is retractable into atube that has an internal diameter that is less than about 0.7 mm, usinga retraction force less than about 2.7 Newtons (0.6 lbf) force. Theforce for retrieving the device 10 into a microcatheter 61 may bebetween about 0.8 Newtons (0.18 lbf) and about 2.25 Newtons (0.5 lbf).

Engagement of the permeable shell 40 with tissue of an inner surface ofa vascular defect 160, when in an expanded relaxed state, may beachieved by the exertion of an outward radial force against tissue ofthe inside surface of the cavity of the patient's vascular defect 160 asshown in FIG. 29. A similar outward radial force may also be applied bya proximal end portion and permeable shell 40 of the device 10 so as toengage the permeable shell 40 with an inside surface or adjacent tissueof the vascular defect 160. Such forces may be exerted in someembodiments wherein the nominal outer transverse dimension or diameterof the permeable shell 40 in the relaxed unconstrained state is largerthan the nominal inner transverse dimension of the vascular defect 160within which the device 10 is being deployed, i.e., oversizing asdiscussed above. The elastic resiliency of the permeable shell 40 andfilaments 14 thereof may be achieved by an appropriate selection ofmaterials, such as superelastic alloys, including nickel titaniumalloys, or any other suitable material for some embodiments. Theconformability of a proximal portion of the permeable shell 40 of thedevice 10 may be such that it will readily ovalize to adapt to the shapeand size of an aneurysm neck 190, as shown in FIGS. 20-22, thusproviding a good seal and barrier to flow around the device. Thus thedevice 10 may achieve a good seal, substantially preventing flow aroundthe device without the need for fixation members that protrude into theparent vessel.

Some implanted device embodiments 10 have the ends of the filaments 14of the permeable shell 40 disposed even with or just within a planeformed by the apices of the filaments disposed adjacent to the ends.Some embodiments of the device 10 may also include a sealing memberdisposed within or about a perimeter zone 198 or other suitable portionof the permeable shell 40 and be configured to facilitate the disruptionof flow, a fibrotic tissue response, or physically form a seal betweenthe permeable shell 40 and a surface of the patient's vasculature. Thesealing member may comprise coatings, fibers or surface treatments asdescribed herein. The sealing member may be in a part or all of an areaof the periphery of the device adjacent where the device contacts thewall of the aneurysm near the aneurysm neck (sealing zone 198) as shownin FIGS. 29 and 30. The zone may extend from about the apex of the outerproximal end radius 88 for a distance up to about 20% of the height ofthe expanded device 10. The sealing zone 198 may include between about5% and 30% of the device 10 surface area. Since the flow of blood intoan aneurysm 160 generally favors one side of the opening, the sealingmember may be incorporated in or attached to the permeable shell 40structure throughout the peripheral area (sealing zone 198) shown inFIG. 30. Some embodiments of the sealing member may include a swellablepolymer. In some embodiments, the sealing member may include orbioactive material or agent such as a biologic material orbiodegradable, bioresorbable or other bioactive polymer or copolymersthereof.

Any embodiment of devices for treatment of a patient's vasculature 10,delivery system 112 for such devices 10 or both discussed herein may beadapted to deliver energy to the device for treatment of a patient'svasculature or to tissue surrounding the device 10 at the implant sitefor the purpose of facilitating fixation of a device 10, healing oftissue adjacent the device or both. In some embodiments, energy may bedelivered through a delivery system 112 to the device 10 for treatmentof a patient's vasculature such that the device 10 is heated. In someembodiments, energy may be delivered via a separate elongate instrument(e.g. catheter, not shown) to the device 10 for treatment of a patient'svasculature and/or surrounding tissue at the site of the implant 154.Examples of energy embodiments that may be delivered include but are notlimited to light energy, thermal or vibration energy, electromagneticenergy, radio frequency energy and ultrasonic energy. For someembodiments, energy delivered to the device 10 may trigger the releaseof chemical or biologic agents to promote fixation of a device fortreatment of a patient's vasculature 10 to a patient's tissue, healingof tissue disposed adjacent such a device 10 or both.

The permeable shell 40 of some device embodiments 10 may also beconfigured to react to the delivery of energy to effect a change in themechanical or structural characteristics, deliver drugs or otherbioactive agents or transfer heat to the surrounding tissue. Forexample, some device embodiments 10 may be made softer or more rigidfrom the use of materials that change properties when exposed toelectromagnetic energy (e.g., heat, light, or radio frequency energy).In some cases, the permeable shell 40 may include a polymer that reactsin response to physiologic fluids by expanding. An exemplary material isdescribed by Cox in U.S. Patent Application No. 2004/0186562, filed Jan.22, 2004, titled “Aneurysm Treatment Device and Method of Use”, which isincorporated by reference herein in its entirety.

Device embodiments 10 and components thereof discussed herein may takeon a large variety of configurations to achieve specific or generallydesirable clinical results. In some device embodiments 10, the start ofthe braided structure of the permeable shell 40 may be delayed from theproximal hub 68 so that the filaments 1 emanate from the proximal hub 68in a spoke-like radial fashion as shown in the proximal end view of adevice in FIG. 31. A flattened analog version of the braid pattern ofFIG. 31 is also shown in FIG. 33. This configuration may result in asmaller width gap between the filaments 14 at a given radial distancefrom the proximal hub 68 relative to a fully braided configuration, theflattened analog pattern of which is shown in FIG. 34. This may providebetter flow disruption and promote hemostasis in the area of the device10 that may be subjected to the highest flow rates. FIG. 32 illustratesa flattened analog representation of a non-braided filament structurefor reference.

The woven structure may include a portion where the weave or braid ofthe filaments 14 is interrupted as shown in a flat pattern analogpattern in FIG. 35. In the interrupted region, the filaments 14 may besubstantially parallel to each other. The interrupted area may provide aregion with different mechanical characteristics such as radialstiffness and/or compliance. Further, the interrupted region may allowfor the addition of non-structural fibers or sealing members 200 asdescribed herein or other elements to facilitate fixation, healing,fibrosis or thrombosis. The interrupted region may be within, part of oradjacent to the sealing member zone 198 as shown in FIGS. 29 and 30. Theinterrupted region may be less than about 50% of the surface area andmay be between about 5% and 25% of the surface area.

In some embodiments, filamentary or fibrous members that aresubstantially non-structural may be attached or interwoven into thestructural filaments of a portion of the permeable shell to increase aresistance to the flow of blood through the permeable shell structure40. In some embodiments, a plurality of fibers 200 may be attached onthe inner surface of the permeable shell 40 near the proximal hub 68 asshown in FIG. 36. The fibrous members 200 may be the fibers that formthe detachment system tether for some embodiments. In some embodiments,one or more fibers 200 may be interwoven into the permeable shellfilaments 14 as shown in FIG. 37. The non-structural fibers 200, whichmay be microfibers or any other suitable fibers, may be polymeric. Thenon-structural fibers 200 may include, but not limited to, any of thefibers or microfibers discussed or incorporated herein.

In some cases, device embodiments for treatment of a patient'svasculature 10 may generally be fabricated by braiding a substantiallytubular braided structure with filamentary elements 14, forming thebraided tubular structure into a desired shape, and heat setting thebraided formed filaments into the desired shape. Once so formed, theends of the elongate resilient filaments 14 may then be secured togetherrelative to each other by any of the methods discussed above andproximal and distal hubs 66 and 68 added.

Such a braiding process may be carried out by automated machinefabrication or may also be performed by hand. An embodiment of a processfor braiding a tubular braided structure by a manual process is shown inFIG. 38. A plurality of elongate resilient filaments 14 are secured atone end of an elongate cylindrical braiding mandrel 202 by aconstraining band 204. The band 204 may include any suitable structurethat secured the ends of the filaments 14 relative to the mandrel 202such as a band of adhesive tape, an elastic band, an annular clamp orthe like. The loose ends of the filaments 14 opposite the secured endsare being manipulated in a braided or woven pattern as indicated by thearrows 206 to achieve a one over-one under braid pattern for generationof a braided tubular member 208. As discussed above, although a oneover-one under simple braid pattern is shown and discussed, other braidor weave patterns may also be used. One such example of another braidconfiguration may include a two over-one under pattern. FIG. 39illustrates the braided tubular member 208 taking shape and lengtheningas the braiding process continues as indicated by the arrows 206 in FIG.39. Once the braided tubular member 208 achieves sufficient length, itmay be removed from the braiding mandrel 202 and positioned within ashaping fixture such as the shaping fixture embodiments shown in FIGS.40 and 41.

FIG. 40 shows the tubular braided member 208 disposed over an internalrod mandrel 210 that extends through central lumens of an internal ballmandrel 212 and a pair of opposed recessed end forming mandrels 214. Thetubular braided member 208 is also disposed over an outer surface of theinternal ball mandrel 212 and within an inner lumen of each of the endforming mandrels 214. In order to hold the braided tubular member 208onto an outer surface contour of the internal ball mandrel 212,including the recessed ends 216 thereof, the end forming mandrels 214are configured to be pushed against and into the recessed ends 216 ofthe internal ball mandrel 212 such that the inside surface of thebraided tubular member 208 is held against the outer contour of theinternal ball mandrel 212 and fixed in place. This entire fixture 220with the inside surface of the braided tubular structure 208 heldagainst the outside surface of the internal ball mandrel 212 may then besubjected to an appropriate heat treatment such that the resilientfilaments 14 of the braided tubular member 208 assume or are otherwiseshape-set to the outer contour of the central ball mandrel 212. In someembodiments, the filamentary elements 14 of the permeable shell 40 maybe held by a fixture configured to hold the permeable shell 40 in adesired shape and heated to about 475-525 degrees C. for about 5-10minutes to shape-set the structure.

The central ball mandrel 212 may be configured to have any desired shapeso as to produce a shape set tubular braided member 208 that forms apermeable shell 40 having a desired shape and size such as the globularconfiguration of the device 10 of FIGS. 3-6 above, or any other suitableconfiguration. As such, the central ball mandrel 212 may also be aglobular-shaped ball with recesses in opposing sides for the hubs 66 and68 that is placed inside the tubular braid 208. A mold or molds thathave one or more pieces that are assembled to form a cavity with thedesired device shape may also be used in conjunction with or in place ofthe end forming mandrels 214. Once the heat set process is complete,fibers, coatings, surface treatments may be added to certain filaments,portions of filaments, or all of the permeable shell 40 structures thatresults. Further, for some embodiments of device processing, thepermeable shell 40 may be formed as discussed above by securing proximalends 60 and distal ends 62 of elongate filamentary elements 14, or torespective proximal and distal hubs 66 and 68.

FIG. 41 shows another embodiment of a fixture for shape setting thepermeable shell 40 of a device for treatment of a patient's vasculature.The fixture embodiment 230 of FIG. 41 may be used in essentially thesame manner as the fixture embodiment 220 of FIG. 40, except thatinstead of a central ball mandrel 212, an internal tube mandrel 232 isused in conjunction with an external tube restraint 234 in order to holdthe shape of the braided tubular member 208 during the heat settingprocess. More specifically, the tubular braided member 208 is disposedover an internal rod mandrel 210 that extends through central lumens ofthe internal tube mandrel 232 and a pair of opposed recessed end formingmandrels 214. The tubular braided member 208 is also disposed over anouter surface of the internal tube mandrel 232 and within an inner lumenof each of the end forming mandrels 214.

In order to hold the braided tubular member 208 into a desired shape,including the recessed ends thereof, the end forming mandrels 214 areconfigured to be pushed against and into recessed ends 238 of theinternal tube mandrel 232 such that the inside surface of the braidedtubular member 208 is held against the outer contour of the internaltube mandrel 232 and fixed in place at the ends of the tube mandrel 232.Between the ends of the tube mandrel 232, the braided tubular member 208radially expands outwardly until it touches and is radially constrainedby an inside surface of an external tube mandrel 234. The combination ofaxial restraint and securement of the braided tubular member 208 at theends of the internal tube mandrel 232 in conjunction with the inwardradial restraint on an outside surface of the braided tubular member 208disposed between the proximal and distal ends thereof, may be configuredto produce a desired globular configuration suitable for the permeableshell 40 of the device 10.

Once again, this entire fixture 230 with the inside surface of the endsof the braided tubular structure 208 held against the outside surface ofthe ends of the internal tube mandrel 232 and an outside surface of thebraided tubular member 208 radially constrained by an inside surface 233of the external tube member 234, may then be subjected to an appropriateheat treatment. The heat treatment may be configured such that theresilient filaments 14 of the braided tubular member 208 assume or areotherwise shape-set to the globular contour of the filaments 14generated by the fixture 230. In some embodiments, the filamentaryelements 14 of the permeable shell 40 may be held by a fixtureconfigured to hold the braided tubular member 208 in a desired shape andheated to about 475-525 degrees C. for about 5-10 minutes to shape-setthe structure. The internal tube mandrel 232 and inside surface 233 ofthe external tube member 234 may be so configured to have any desiredshape so as to produce a shape set tubular braided member 208 that formsa permeable shell 40 having a desired shape and size such as theglobular configuration of the device of FIGS. 3-6 above, or any othersuitable configuration.

As shown, the arced portion of the filaments 1110 may have asinusoidal-like shape with a first or outer radius 1126 and a second orinner radius 1128 near a first end of the permeable shell as shown inFIG. 42. This sinusoid-like shape may provide a concavity in theproximal end that may reduce the obstruction of flow in the parentvessel. For some embodiments, the first radius and second radius of thepermeable shell may be between about 0.12 mm to about 3 mm. For someembodiments, the distance between the first end and second end may beless than about 60% of the overall length of the permeable shell 1106for some embodiments. Such a configuration may allow for the second endto flex downward toward the first end when the device meets resistanceat the distal end and thus may provide longitudinal conformance. Thefilaments 1110 may be shaped in some embodiments such that there are noportions that are without curvature over a distance of more than about 2millimeters. Thus, for some embodiments, each filament 1110 may have asubstantially continuous curvature. This substantially continuouscurvature may provide smooth deployment and may reduce the risk ofvessel perforation. For some embodiments, one of the ends may beretracted or everted to a greater extent than the other so as to be morelongitudinally or axially conformal than the other end.

The first radius 1126 and second radius 1128 of the permeable shell 1106may be between about 0.12 mm to about 3 mm for some embodiments. Forsome embodiments, the distance between the first end 1112 and second end1114 may be less than about 60% of the overall length of the supportstructure. A gap between the hubs at the first end and second end mayallow for the distal or second end hub to flex downward toward theproximal or first end hub 1112 when the device meets resistance at thedistal end and thus provides longitudinal conformance. The filaments1110 may be shaped such that there are no portions that are withoutcurvature over a distance of more than about 2 millimeters. Thus, forsome embodiments, each filament 1110 may have a substantially continuouscurvature. This substantially continuous curvature may provide smoothdeployment and may reduce the risk of vessel perforation. The distal orsecond end 1104 may be retracted or everted to a greater extent than theproximal end such that the distal end portion of the permeable shell maybe more radially conformal than the proximal end portion. Conformabilityof a distal end portion may provide better device conformance toirregular shaped aneurysms or other vascular defects. A convex surfaceof the device may flex inward forming a concave surface to conform tocurvature of a vascular site.

FIG. 43 shows an enlarged view of the filaments 1110 disposed within afirst hub 1112 or end portion of the device 100 with the filaments 1110constrained and tightly packed by an outer ring 1132 of the first hub. Atether member 134 may be disposed within a middle portion of thefilaments 1110. Such a tether 1134 may be a dissolvable, severable orreleasable tether that may be part of a release mechanism 1124 used todeploy the device 1100. FIGS. 43A-E illustrate various embodiments offirst ends or hubs 112 showing the configuration of filaments 1110,mandrels 1136, tethers and the like which may be tightly packed andradially constrained by respective outer ring members 1132. In someembodiments, the braided or woven structure may be constructed using alarge number of small filaments. The number of filaments may be greaterthan 1125 and may be between 80 and 180. In some embodiments, thebraided structure of the permeable shell may be constructed with two ormore sizes of filaments. For example, the structure may have severallarger filaments 1138 that provide structural support and severalsmaller filaments 1110 that provide the desired pore size and densityand thus flow resistance. For some embodiments, smaller filaments 1110may have a transverse dimension or diameter of about 0.015 mm to about0.05 mm and larger filaments 1138 may have a transverse dimension ordiameter of about 0.04 mm to about 0.1 mm. The filaments may be braidedin a plain weave that is one under, one over structure or asupplementary weave; more than one warp interlace with one or more thanone weft. The pick count may be varied between about 25 and 200 picksper inch (PPI).

FIG. 43A illustrates a transverse section of a first hub portion havinga center mandrel 1136 disposed within 8 larger filaments 1138 which aredisposed within and in contact with a plurality of small filaments 1110.There are substantially three circumferential rings of small filamentsdisposed between the larger filaments and the inner surface of the outerring. The small filaments 1110 are disposed within and 30 radiallyconstrained by the outer ring 132. Once the first hub is formed, thecentral mandrel 1136 may be removed with a releasable tether disposed inits place. The embodiment of FIG. 43B has a configuration similar tothat of the embodiment of FIG. 43A but with substantially 4circumferential rings of smaller filaments 1110 disposed between thelarger filaments 1138 and the inner surface of the outer ring. Theembodiment of FIG. 43C includes a configuration similar to that of FIG.43A but with larger filaments 1138 disposed between a single innercircumferential ring of smaller filaments 1110 which are disposedbetween a mandrel and the larger filaments 1138. A singlecircumferential ring of smaller filaments is disposed between the larger5 filaments and the inner surface of the outer ring. FIG. 43D shows anembodiment of a first hub having a configuration similar to that of theembodiment of FIG. 43C but with two circumferential rings of smallerfilaments 1110 disposed between the larger filaments and an innersurface of an outer ring. FIG. 43E illustrates another embodiment whichincludes small filaments 1110 disposed radially within a plurality of 10larger filaments 1140 with yet another ring of smaller filamentsdisposed radially outside the larger filaments. All filaments of theembodiment of FIG. 43E are disposed within and constrained by an outerring 1132 which may be configured to secure the large and smallfilaments in place relative to each other within the outer ring.

For some embodiments, material may be attached to filaments 14 of thepermeable shell 40 of a device 10 such that it substantially reduces thesize of the fenestrations, cells or pores 64 between filaments 14 andthus reduces the porosity in that area. For example, coating embodimentsmay be disposed on portions of the filaments 14 to create smallfenestrations or cells and thus higher density of the permeable shell40. Active materials such as a responsive hydrogel may be attached orotherwise incorporated into permeable shell 40 of some embodiments suchthat it swells upon contact with liquids over time to reduce theporosity of the permeable shell 40.

Device embodiments 10 discussed herein may be coated with variouspolymers to enhance it performance, fixation and/or biocompatibility. Inaddition, device embodiments 10 may be made of various biomaterialsknown in the art of implant devices including but not limited topolymers, metals, biological materials and composites thereof. Deviceembodiments discussed herein may include cells and/or other biologicmaterial to promote healing. Device embodiments discussed herein mayalso be constructed to provide the elution or delivery of one or morebeneficial drugs, other bioactive substances or both into the blood orthe surrounding tissue.

Permeable shell embodiments 40 of devices for treatment of a patient'svasculature 10 may include multiple layers. A first or outer layer maybe constructed from a material with low bioactivity andhemocompatibility so as to minimize platelet aggregation or attachmentand thus the propensity to form clot and thrombus. Optionally, an outerlayer may be coated or incorporate an antithrombogenic agent such asheparin or other antithrombogenic agents described herein or known inthe art. One or more inner layers disposed towards the vascular defectin a deployed state relative to the first layer may be constructed ofmaterials that have greater bioactivity and/or promote clotting and thusenhance the formation of an occlusive mass of clot and device within thevascular defect. Some materials that have been shown to have bioactivityand/or promote clotting include silk, polylactic acid (PLA),polyglycolic acid (PGA), collagen, alginate, fibrin, fibrinogen,fibronectin, Methylcellulose, gelatin, Small Intestinal Submucosa (SIS),poly-N-acetylglucosamine and copolymers or composites thereof.

Bioactive agents suitable for use in the embodiments discussed hereinmay include those having a specific action within the body as well asthose having nonspecific actions. Specific action agents are typicallyproteinaceous, including thrombogenic types and/or forms of collagen,thrombin and fibrogen (each of which may provide an optimal combinationof activity and cost), as well as elastin and von Willebrand factor(which may tend to be less active and/or expensive agents), and activeportions and domains of each of these agents. Thrombogenic proteinstypically act by means of a specific interaction with either plateletsor enzymes that participate in a cascade of events leading eventually toclot formation. Agents having nonspecific thrombogenic action aregenerally positively charged molecules, e.g., polymeric molecules suchas chitosan, polylysine, poly(ethylenimine) or acrylics polymerized fromacrylimide or methacrylamide which incorporate positively-charged groupsin the form of primary, secondary, or tertiary amines or quarternarysalts, or non-polymeric agents such as (tridodecylmethylammoniumchloride). Positively charged hemostatic agents promote clot formationby a non-specific mechanism, which includes the physical adsorption ofplatelets via ionic interactions between the negative charges on thesurfaces of the platelets and the positive charges of the agentsthemselves.

Device embodiments 10 herein may include a surface treatment or coatingon a portion, side or all surfaces that promotes or inhibits thrombosis,clotting, healing or other embolization performance measure. The surfacetreatment or coating may be a synthetic, biologic or combinationthereof. For some embodiments, at least a portion of an inner surface ofthe permeable shell 40 may have a surface treatment or coating made of abiodegradable or bioresorbable material such as a polylactide,polyglycolide or a copolymer thereof. Another surface treatment orcoating material which may enhance the embolization performance of adevice includes a polysachharide such as an alginate based material.Some coating embodiments may include extracellular matrix proteins suchas ECM proteins. One example of such a coating may be Finale Prohealingcoating which is commercially available from Surmodics Inc., EdenPrairie, Minn. Another exemplary coating may be Polyzene-F which iscommercially available from CeloNovo BioSciences, Inc., Newnan, Ga. Insome embodiments, the coatings may be applied with a thickness that isless than about 25% of a transverse dimension of the filaments 14.

Antiplatelet agents may include aspirin, glycoprotein IIb/IIIa receptorinhibitors (including, abciximab, eptifibatide, tirofiban, lamifiban,fradafiban, cromafiban, toxifiban, XV454, lefradafiban, klerval,lotrafiban, orbofiban, and xemilofiban), dipyridamole, apo-dipyridamole,persantine, prostacyclin, ticlopidine, clopidogrel, cromafiban,cilostazol, and nitric oxide. To deliver nitric oxide, deviceembodiments may include a polymer that releases nitric oxide. Deviceembodiments 10 may also deliver or include an anticoagulant such asheparin, low molecular weight heparin, hirudin, warfarin, bivalirudin,hirudin, argatroban, forskolin, ximelagatran, vapiprost, prostacyclinand prostacyclin analogues, dextran, synthetic antithrombin, Vasoflux,argatroban, efegatran, tick anticoagulant peptide, Ppack, HMG-CoAreductase inhibitors, and thromboxane A2 receptor inhibitors.

In some embodiments, the permeable shell 40 of a device 10 may be coatedwith a composition that may include nanoscale structured materials orprecursors thereof (e.g., self-assembling peptides). The peptides mayhave with alternating hydrophilic and hydrophobic monomers that allowthem to self-assemble under physiological conditions. The compositionmay comprise a sequence of amino acid residues. In some embodiments, thepermeable shell may include a thin metallic film material. The thin filmmetal may be fabricated by sputter deposition and may be formed inmultiple layers. The thin film may be a nickel-titanium alloy also knownas nitinol.

With regard to the above detailed description, like reference numeralsused therein refer to like elements that may have the same or similardimensions, materials and configurations. While particular forms ofembodiments have been illustrated and described, it will be apparentthat various modifications can be made without departing from the spiritand scope of the embodiments of the invention. Accordingly, it is notintended that the invention be limited by the forgoing detaileddescription.

What is claimed is:
 1. A method of treating a cerebral aneurysm within acerebral vasculature of a patient, comprising the steps of: providing amicrocatheter having a proximal end, a distal end, and a lumentherebetween; providing a device for treatment of an aneurysm within apatient's vasculature, comprising: a self-expanding resilient permeableshell having a proximal end, a distal end, a longitudinal axis andfurther comprising: a plurality of elongate resilient filaments with awoven structure, wherein the plurality of filaments includes smallfilaments and large filaments, wherein the small filaments have atransverse dimension smaller than the transverse dimension of the largefilaments, the woven structure having a radially constrained elongatedstate configured for delivery within a microcatheter with the thin wovenfilaments extending longitudinally from the proximal end to the distalend radially adjacent each other along a length of the filaments,wherein the filaments are bundled and secured to each other at aproximal end, wherein a ratio of the total cross-sectional area of smallfilaments to the total cross-sectional area of large filaments isbetween 0.56 and 1.89, and advancing the distal end of the microcatheterto a region of interest within a cerebral artery; advancing the devicethrough the lumen and out of the distal end of the microcatheter suchthat the permeable shell deploys within the cerebral aneurysm, whereinthe permeable shell expands to an expanded state within the cerebralaneurysm, the expanded relaxed state having a longitudinally shortenedconfiguration relative to the radially constrained state; andwithdrawing the microcatheter from the cerebral artery, wherein thepermeable shell is the only implant delivered into the cerebral aneurysmthrough the microcatheter before the microcatheter is withdrawn.
 2. Themethod of claim 1, wherein the permeable shell forms a generallyspherical shape when in the expanded relaxed state.
 3. The method ofclaim 1, wherein the permeable shell forms a generally ovoid shape whenin the expanded relaxed state.
 4. The method of claim 1, wherein thepermeable shell forms a generally globular shape when in the expandedrelaxed state.
 5. The method of claim 1, wherein the woven structure isadapted to reside within the aneurysm.
 6. The method of claim 5, whereinthe device is adapted to span the neck of the aneurysm.
 7. The method ofclaim 1, wherein, after implantation, no part of the device extends overthe aneurysm neck outside of the dome.
 8. The method of claim 1, whereinthe smaller filaments have a transverse diameter of about 0.015 mm toabout 0.05 mm.
 9. The method of claim 1, wherein the larger filamentshave a transverse diameter of about 0.04 mm to about 0.1 mm.
 10. Themethod of claim 1, wherein the filaments are bundled and secured to eachother at a distal end.
 11. The method of claim 1, wherein the ratio ofthe total cross-sectional area of small filaments to the totalcross-sectional area of large filaments is between 1.21 and 1.89. 12.The method of claim 1, wherein the ratio of the total cross-sectionalarea of small filaments to the total cross-sectional area of largefilaments is between 1.06 and 1.89.